مروری بر 150 بیماری غربالگری شده در پانل کاریر اسکرینینگ


مروری بر 150 بیماری غربالگری شده در پانل کاریر اسکرینینگ

  مشخصات حدود 150 بیماری غربالگری شده در پانل کاریر اسکرینینگ به پیوست جدول ذیل آمده است.

غربالگری ناقلین (‏carrier Screening‏) اصطلاحی است که برای توصیف یک تست ژنتیک استفاده می شود 

که بر روی افراد ‏بدون علامت انجام شده

 تا مشخص شود که یک موتاسیون و یا یک آلل غیرطبیعی که منجر به ایجاد یک بیماری خاص می شود را ‏دارد یا خیر. ‏

این غربالگری برای یک بیماری خاص و یا چندین بیماری بطور همزمان انجام می شود.‏

بطور کلی غربالگری ناقلین به منظور تشخیص وضعیت ناقلی در بیماران بدون علامت برای:‏

غربالگری بیماریهای ژنتیکی مغلوب (چه بصورت اتوزوم مغلوب -‏Autosomal recessive ‌‏ - و چه وابسته به کروموزوم ‏X‏ ‏مغلوب –   ‏X linked recessive ‌‏ -) در زوجهایی بدون علامتی که هیچگونه ریسک اولیه افزایش یافته ای برای داشتن یک ‏وضعیت ناقلی برای بیماری خاص طبق سوابق فامیلی خود و یا زوج شان ندارند مورد استفاده قرار می گیرد.‏

بطور کلی 1300 بیماری در این دو گروه از بیماریهای ژنتیکی قرار می گیرند. 

میزان بروز این بیماریها در نوزادان تازه متولد ‏شده در کل جامعه بین 2 الی 3 درصد می باشد که این میزان در ازدواج های فامیلی به 2 الی 3 برابر ‏general population‏ ‏می رسد (یعنی میزان شیوع در ازدواج های فامیلی به 6 الی 8 درصد می رسد).‏





Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

1

Abetalipoproteinemia

MTTP

Celiac syndrome, Pigmentary degeneration of the retina, Progressive ataxic neuropathy, peculiar 'burr-cell' malformation of the red cells called Acanthocytosis, Pes cavus, Clubfoot and Lordosis or Kyphosis

AR




2

Adenosine Deaminase Deficiency

ADA

Failure to thrive, Sinusitis, Asthma, Pneumonia, Hepatosplenomegaly, Diarrhea, Mesangial sclerosis, Platyspondyly, Pelvic dysplasia, Eosinophilia, Lymphopenia, B-cell lymphoma and Autoimmune hemolytic anemia.

AR




3

Adrenoleukodystrophy, X-Linked

ABCD1

Hearing loss, Loss of vision, Fecal incontinence, Urinary incontinence, Progressive neurodegeneration, Dementia, Spasticity, Paraparesis, Seizures, Ataxia, Cerebral demyelination and adrenomyeloneuropathy

XLR




4

Alpha-Mannosidosis

MAN2B1

Growth retardation, Macrocephaly, Flat occiput, Coarse facies, Frontal bossing, Prognathism, Large ears, Flat nose, Macroglossia, Gingival hypertrophy, Pectus carinatum, Spondylolisthesis, Bowed femurs, Hypotonia, Ataxia, Spasticity, Nystagmus and Cerebral atrophy

AR




5

Alpha-Thalassemia Mental Retardation Syndrome

ATRX

Short stature, Growth retardation, Microcephaly, Dolichocephaly, Micrognathia, Bitemporal narrowing, Hypertelorism, Ptosis, Macrostomia, Protruding tongue, Gut dysmotility, Hypogonadism, Kyphoscoliosis, Genua valga, Brachydactyly, Pes planus and Mental retardation.

XLD




6

Alport Syndrome

COL4A3

Hematuria, Proteinuria, Myopia, Hearing loss, Lens opacities, Hypertension, Corneal erosions, Glomerulonephropathy, Leiomyomatosis, Cataracts, and Aortic dissection

AR




COL4A5

XLR




7

Alstrom Syndrome

ALMS1

Short stature, Truncal obesity, Otitis media, Hearing loss, Pigmentary retinopathy, Photophobia, Nystagmus, Congestive heart failure, Atherosclerosis, Asthma, Gynecomastia, Hepatomegaly, Renal failure, Kyphosis, Scoliosis, Alopecia and Pes planus.

AR




8

Ataxia-Telangiectasia

ATM

Ataxia, Telangiectasia, Chorea, Myoclonus, Neuropathy, Short stature, Sinusitis, Hypogonadism, Cafe-au-lait spots, Delayed puberty, Diabetes mellitus, Oculomotor apraxia, Chronic lung infections, increased risk of developing Leukemia and Lymphoma.

AR




9

Argininosuccinic Aciduria

ASL

Failure to thrive, Hepatomegaly, Protein avoidance, Vomiting, Dry brittle hair, Ataxia, Seizures, Coma, Cerebral edema, Developmental delay, Mental retardation, Irritability and Lethargy.

AR




10

Aromatase Deficiency

CYP19A1

Primary Amenorrhea, Tall stature, Osteoporosis, Osteopenia, Pseudohermaphroditism, Clitoromegaly and Polycysitic ovaries (in females), T2DM, Obesity and Hyperinsulinemia (in males).


AR




11

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

SACS

Pes cavus, Hammer toes, Hyperreflexia, Distal muscle weakness, Spasticity, Ataxia, Amyotrophy, Nystagmus, Dysarthria, Hypermyelination of the retina and Mitral valve prolapse (rare).


AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

12

Arts syndrome

PRPS1

Poor growth, Hearing impairment, Optic atrophy, Loss of vision, Nystagmus, Drooling, Recurrent respiratory tract infections, Dysphagia, Neonatal hypotonia, Progressive muscle weakness, Mental retardation, Ataxia, Seizures and Immune deficiency





13

Bardet-Biedl Syndrome 10

BBS10

Obesity, Retinitis pigmentosa, Retinal degeneration, Strabismus, Cataracts, High arched palate, Dental crowding, Hypodontia, Small tooth roots, Hypogonadism, Renal anomalies and Polydactyly.

AR




14

Bardet-Biedl Syndrome 2

BBS2

AR




15

Bardet-Biedl Syndrome 12

BBS12

AR




16

Bardet-Biedl Syndrome 13

MKS1(BBS13)

AR




17

Beta-Globin-Related Hemoglobinopathies: Beta-Thalassemia

HBB

Splenomegaly, Hypochromic anemia, Gallstones, Skeletal abnormalities, Liver cirrhosis, Liver fibrosis and Osteoporosis


AR




18

3-Beta-Hydroxysteroid Dehydrogenase Type II Deficiency

HSD3B2

Ambiguous genitalia, Salt-wasting disorder, Hypospadias, Bifid scrotum, Absent scrotum, Micropenis and Clitoris-like phallus.

AR




19

Beta-Ketothiolase Deficiency

ACAT1

Vomiting, Dehydration, Difficulty breathing, Slight scoliosis, Dyspnea, Tachypnoea, Hypotonia, Extreme tiredness (Lethargy) and Seizures

AR




20

Biotinidase Deficiency

BTD

Seizures, Ataxia, Hypotonia, Alopecia, Periorificial cutaneous eruption, Episodic metabolic acidosis, Hearing loss, Loss of vision, Developmental delay, Lactic academia and Propionic academia.

AR




21

Bloom Syndrome

BLM

Growth failure, Dolichocephaly, Microcephaly, Malar hypoplasia, Prominent nose, Chronic lung disease, Bronchiectasis, Azoospermia, Cryptorchidism, Syndactyly, Polydactyly, Facial telangiectasia, Cafe-au-lait spots, Hypertrichosis and Learning disability

AR




22

Canavan Disease

ASPA

Increased head circumference, Deafness, Optic atrophy, Nystagmus, Blindness, Generalized seizures, Initial hypotonia followed by spasticity, Opisthotonus and Brain atrophy.

AR




23

Carnitine Palmitoyltransferase IA Deficiency

CPT1A

Cardiomegaly, Cardiac rhythm disturbances, Hepatomegaly, Poor feeding, Diarrhea, Hypotonia, Lethargy, Seizures, Coma, Hypoglycemia, Encephalopathy and Renal tubular acidosis.

AR




24

Carnitine Palmitoyltransferase II Deficiency

CPT2

Muscular pain, Rhabdomyolysis, Myoglobinuria, Cold or febrile illness, Elevation of creatine kinase, Renal failure, Muscle stiffness and Muscle cramps.

AR




25

Carpenter Syndrome

RAB23

Short stature, Brachycephaly, Abnormalities of the fingers, Cloverleaf skull, Midface hypoplasia, Low-set ears, Conductive hearing loss, Sensorineural hearing loss, Microcornea, Optic atrophy, Flat nasal bridge, High-arched palate, Missing teeth, Atrial septal defect, Umbilical hernia.

AR




26

Charcot-Marie-Tooth Disease, Type 5

PRPS1

Sensorineural hearing loss, Vision impairment, Optic nerve atrophy, Retinitis pigmentosa, Pes cavus, Delayed motor development, Distal limb muscle atrophy, Segmental demyelination and Onion bulb formations


XLR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

27

Chronic Granulomatous Disease

CYBA

Pneumonia due to immunodeficiency, Hepatic abscesses due to immunodeficiency, Hepatomegaly, Splenomegaly, Perirectal abscesses due to immunodeficiency, Osteomyelitis, Dermatitis, Cellulitis due to immunodeficiency, Lymphadenitis, Bacterial and Fungal infections.

AR




28

Citrin Deficiency

SLC25A13

Potentially lethal coma, Failure to thrive, Cirrhosis, Convulsions, Hyperammonemia, Hypercitrullinemia, Orotic aciduria, and Brain edema, Coma, Pancreatitis and Hepatocyte ballooning

AR




29

Citrullinemia, Type 1

ASS1

Potentially lethal coma, Failure to thrive, Cirrhosis, Convulsions, Hyperammonemia, Hypercitrullinemia, Orotic aciduria, and Defective activity of argininosuccinate synthetase


AR




30

Cohen Syndrome

VPS13B

Short stature, Truncal obesity, Microcephaly, Short philtrum, Mild micrognathia, Facial hypotonia, Myopia, Optic atrophy, Prominent nasal bridge, High narrow palate, Open mouth appearance, Mitral valve prolapse, Genu valgum, Cubitus valgus, Narrow feet, Mental retardation, Cerebellar hypoplasia

AR




31

Combined Malonic and Methylmalonic Aciduria

ACSF3

Dehydration, Diarrhea, Failure to thrive, Seizures, Global developmental delay, Ketoacidosis, Methylmalonic aciduria, Vomiting, dystonia, hypoglycemia, microcephaly, Lethargy.

AR




32

Congenital Adrenal Hyperplasia due to 17-Alpha-Hydroxylase Deficiency

CYP17A1

Ambiguous genitalia, Primary amenorrhea, Male pseudohermaphroditism, Hypertension, Hypokalemic alkalosis, Gynecomastia, Adrenogenital syndrome and Hypospadias

AR




33

Congenital Amegakaryocytic Thrombocytopenia

MPL

Hypoplastic cerebellar vermis, Severe thrombocytopenia, Pancytopenia, Megakaryocytopenia, Elevated serum thrombopoietin and Abnormal hemoglobin


AR




34

Congenital Insensitivity to Pain with Anhidrosis

NTRK1

Absent corneal sensation, Corneal opacities, Corneal ulceration, Osteomyelitis, Anhidrosis, Skin ulcers, Dystrophic nails, Hypotrichosis of the scalp, Developmental delay, Mental retardation, Severe episodic fever, Autonomic dysfunction, Irritability and Self-injurious behavior

AR




35

Cystic Fibrosis

CFTR

Failure to thrive, Cor pulmonale, Chronic bronchopulmonary infection, Bronchiectasis, Asthma, Pulmonary blebs, Pseudomonas colonization, Pancreatic insufficiency, Biliary cirrhosis, Meconium ileus (rarely), Rectal prolapse and Male infertility (CBAVD).

AR




36

Corticosterone Methyloxidase Deficiency

CYP11B2

Failure to thrive, Growth retardation, Salt-wasting, Dehydration, Hypotension, Hypoaldosteronism, muscle weakness, fatigue, Vomiting, Seizures, Coma, Poor feeding and Intermittent fever


AR




37

Duchenne Muscular Dystrophy/Becker Muscular Dystrophy

DMD

Cardiomyopathy, Congestive heart failure, Respiratory failure, Scoliosis, Flexion contractures, Calf muscle pseudohypertrophy, Hypotonia, Waddling gait, Hyporeflexia, Positive Gowers sign and Cognitive impairment

XLR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

38

Ellis-van Creveld Syndrome

EVC

Short-limb dwarfism, Normocephaly, Partial cleft lip, Hypodontia, Delayed eruption, Atrial septal defect, Single atrium, Narrow chest, Pectus carinatum, Epispadias, Hypospadias, Cryptorchidism, Genu valgum, Postaxial polydactyly, Talipes equinovarus and Nail dysplasia


AR




39

Emery-Dreifuss Myopathy 1

EMD

Cardiac conduction defects, Atrial arrhythmias, Atrioventricular block, Pectus excavatum, Contracture of elbows and Achilles tendon, Waddling gait and Tendency to walk on toes


XLR




40

Fabry Disease

GLA

Angiokeratomas of the skin, Episodic pain in the extremities, Hypohidrosis, Corneal and lenticular opacities, Postprandial pain and Diarrhea, Neuropathy, Renal disease, Coronary and cerebral vascular disease, Delayed puberty, Renal failure, Hypertension and Angina





XLR




41

Factor IX Deficiency

F9

easy bruising, urinary tract bleeding (hematuria), epistaxis, hemarthrosis, spontaneous bleeding episodes, synovitis and arthropathy

XLR




42

Familial Dysautonomia

IKBKAP

Poor growth, Alacrima, Decreased corneal reflex, Corneal ulceration, Hypertension, Feeding difficulties, Poor oral coordination, Gastroesophageal reflux, Vomiting crises, Diarrhea, Constipation, Glomerulosclerosis, Scoliosis, Acrocyanosis, Hypotonia and Neuropathic arthropathy


AR




43

Familial Hypercholesterolemia

LDLR

Corneal arcus, Xanthelasma, Coronary artery disease and Tendinous xanthomas

AD




44

Familial Hyperinsulinism

ABCC8

Large for gestational age, diffuse Islet cell hyperplasia, Focal adenomatous hyperplasia of beta cells, Loss of consciousness, Hypoglycemic seizures, Cardiomegaly, Mental retardation and Hypoglycemia

AR




KCNJ11

AR




45

Familial Mediterranean Fever

MEFV

Pericarditis, Pleuritis, Hepatomegaly, Splenomegaly, Peritonitis, Abdominal pain, orchitis, Renal amyloidosis, Renal failure, Skin rash, Arthralgia, Meningitis and episodic fever

AR




46

Fanconi Anemia, Group A

FANCA

Small stature, Microcephaly, Ear anomaly, Deafness, Anemia, Strabismus, Microphthalmia, Congenital heart defect, Cryptorchidism, Kidney malformation, Renal ectopia, Radial aplasia, Thumb deformity, Anemic pallor, Bruisability, Hyperpigmentation, Cafe-au-lait spots and Mental retardation


AR




47

Fanconi Anemia, Group C

FANCC

AR




48

Fanconi Anemia, Group G

FANCG

AR




49

Fumarase Deficiency

FH

Failure to thrive, Macrocephaly, Frontal bossing, Hypertelorism, Optic pallor, Optic atrophy, Depressed nasal bridge, Anteverted nares, High-arched palate, Liver failure, Cholestasis, Fibrosis, Hypotonia, Mental retardation, Cerebral atrophy, Polymicrogyria and Seizures

AR




50

Galactokinase Deficiency

GALK1

Cataracts, Pseudotumor cerebri, Galactosuria, Galactosemia, Increased intracranial pressure and Prolonged neonatal jaundice

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

51

Galactosemia

GALT

Failure to thrive, Cataract, Hepatomegaly, Progressive decreased liver function, Cirrhosis, Vomiting, Diarrhea, Ovarian failure due to hypergonadotropic hypogonadism , Hemolytic anemia, Mental retardation (if untreated) and Speech abnormality (if untreated).

AR




52

Gaucher Disease

GBA

Brown accumulation of Gaucher cells at corneoscleral limbus, Macular atrophy, Perimacular grayness, Epistaxis, Pulmonary hypertension, Dyspnea, Restrictive impairment, Hepatomegaly, Splenomegaly, Osteolytic lesions, Osteonecrosis, Thrombocytopenia and Hyperpigmentation

AR




53

Glutaric Acidemia, Type I

GCDH

Failure to thrive, Macrocephaly, Hepatomegaly, Dystonia, Hypotonia, Rigidity, Choreoathetosis, Opisthotonus, Spastic diplegia, Frontotemporal atrophy, Delayed myelination, Hypodensity of lenticular nuclei, Hypodensity of caudate and Striatal necrosis

AR




54

Glutaric Acidemia, Type IIa

ETFA

Renal cortical cysts, Polycystic kidneys, Genital defects, Facial dysmorphism, Macrocephaly, High forehead, Flat nasal bridge, Congenital cataract, Telecanthus, Hypoglycemic coma, Muscle weakness, Muscular hypotonia, Jaundice, Nausea, Vomiting, Hepatomegaly and Hepatic periportal necrosis


AR




55

Glutaric Acidemia, Type IIc

ETFDH

Renal cortical cysts, Polycystic kidneys, Genital defects, Facial dysmorphism, Macrocephaly, High forehead, Flat nasal bridge, Congenital cataract, Telecanthus, Hypoglycemic coma, Muscle weakness, Muscular hypotonia, Jaundice, Nausea, Vomiting, Hepatomegaly and Hepatic periportal necrosis

AR




56

Glycogen Storage Disease, Type Ia

G6PC

Short stature, Delayed puberty, 'Doll-like' facies, Lipemia retinalis, Hypertension, Protuberant abdomen, Liver adenomas, Hepatocellular carcinoma, Hepatomegaly, Pancreatitis, Intermittent diarrhea, Renal stones, Osteoporosis, Gouty arthritis, Xanthoma and Hypoglycemia


AR




57

Glycogen Storage Disease, Type Ib

SLC37A4

Short stature, Delayed puberty, 'Doll-like' facies, Lipemia retinalis, Hypertension, Protuberant abdomen, Liver adenomas, Hepatocellular carcinoma, Hepatomegaly, Pancreatitis, Intermittent diarrhea, Renal stones, Osteoporosis, Gouty arthritis, Xanthoma and Hypoglycemia

AR




58

Glycogen Storage Disease, Type II

GAA

Hearing loss, Macroglossia, Cardiomegaly, Wolf-Parkinson-White syndrome, Cerebral artery aneurysm, Dyspnea, Hepatomegaly, Splenomegaly, Hypotonia, Firm muscles and Absent deep tendon reflexes





59

Glycogen Storage Disease, Type IV / Adult Polyglucosan Body Disease

GBE1

Failure to thrive, Cardiomyopathy, Ascites, Cirrhosis, Hepatosplenomegaly, Esophageal varices, Multiplex arthrogryposis, Muscle weakness, Muscle atrophy, Hypotonia and Portal hypertension

AR




60

Glycogen Storage Disease, Type V

PYGM

Myoglobinuria, Dark urine following exercise, Skeletal muscle weakness, Decreased exercise capacity, Muscle pain and cramps and Rhabdomyolysis

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

61

Glycogen Storage Disease, Type VII

PFKM

Gallstones due to hemolytic anemia, Gout due to increased uric acid, Jaundice due to hemolytic anemia, Exercise intolerance, Muscle weakness, Muscle cramps, Increased muscle glycogen content and Hemolytic anemia

AR




62

GRACILE Syndrome and Other BCS1L-Related Disorders

BCS1L

Intrauterine growth retardation, Failure to thrive, Lactic acidosis, Aminoaciduria, Cirrhosis, Cholestasis, Iron overload, Anhidrosis, Pili torti, Loss of hair, Hepatic steatosis and Hearing impairment

AR




63

GM1 Gangliosidosis

GLB1

Dwarfism, Coarse facies, Flat nose, Hypertelorism, Clear cornea, Cherry-red spot, Gingival hyperplasia, Short neck, Dilated cardiomyopathy, Thick ribs, Inguinal hernia, Hepatosplenomegaly, Kyphosis, Scoliosis, Joint stiffness, Dermal melanocytosis, Hypertrichosis and Mongolian spots.


AR




64

Hemochromatosis, Type 2A

HFE2

Heart failure, Arrhythmia, Dilated cardiomyopathy, Cirrhosis, Liver fibrosis, Hepatomegaly, Splenomegaly, Arthritis, Hyperpigmentation, Lethargy, Hypogonadism, Amenorrhea (females) and Azoospermia (males).

AR




65

Hereditary Fructose Intolerance

ALDOB

Failure to thrive, Absent dental caries, Hepatomegaly, Hepatic steatosis, Cirrhosis, Vomiting, Nausea, Malnutrition, Abdominal pain, Jaundice, Lethargy, Seizures, Coma, Mental retardation and Lactic acidosis

AR




66

HMG-CoA Lyase Deficiency

HMGCL

Microcephaly, Tachydyspnea, Kussmal breathing, Hepatomegaly, vomiting, Paleness, Hypotonia, Refusal of nutrition, Seizures, Spasticity, White matter abnormalities, Abnormal EEG, Somnolence and Anemia


AR




67

Holocarboxylase Synthetase Deficiency

HLCS

Tachypnea, Hyperventilation, Feeding problems, Vomiting, Skin rash, Alopecia, Irritability, Hypotonia, Seizures, Lethargy, Developmental delay, Coma, Hypertonia, Thrombocytopenia and Metabolic acidosis.

AR




68

Homocystinuria

CBS

Ectopia lentis, Vascular occlusive disease, Osteoporosis, Accumulation of homocystine and methionine and defective activity of cystathionine synthase.

AR




69

Homocystinuria due to MTHFR Deficiency

MTHFR

Microcephaly, Muscle weakness, Developmental delay, Seizures, Gait abnormalities, Incoordination, Paresthesias, Stroke and Psychiatric disturbances


AR




70

Homocystinuria, cblE Type

MTRR

Failure to thrive, Nystagmus, Blindness, Hypotonia, Delayed psychomotor development, Hypotonia, Abnormal gait, Seizures, Cerebral atrophy and Megaloblastic anemia.


AR




71

Hypohidrotic Ectodermal Dysplasia 1

EDA

Hypohidrosis , Anhidrosis, Eczema, Spoon-shaped nails, Hypotrichosis, Scanty hair, Hypoplastic maxilla, Small chin, Prominent supraorbital ridge, Periorbital wrinkles, Absent tears, Small nose, Hypoplastic alae nasi, Ozena, Prominent lips, Hypodontia, Microdontia, Conical teeth and Taurodontism

XLR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

72

Hypophosphatasia

ALPL

Short limb dwarfism, Failure to thrive, Blue sclera, Apnea, Short ribs, Rachitic rosary, Rib fractures, Anorexia, Vomiting, Constipation, Nephrocalcinosis, Lack of ossification, Fractures, Platyspondyly, Micromelia, Osteogenesis defect, Seizures, Hypotonia, Irritability and Polyhydramnios


AR




73

Isovaleric Acidemia

IVD

Feeding refusal, Vomiting, Developmental delay, Lethargy, Seizures, Coma, Cerebellar hemorrhage, Metabolic acidosis, Thrombocytopenia, Leukopenia, Pancytopenia and Hypoplastic bone marrow.


AR




74

Krabbe Disease

GALC

Failure to thrive, Deafness, Blindness, Optic atrophy, Nystagmus, Vomiting, Hyperirritability, Hypersensitive to stimuli, Neurodegeneration, Progressive spasticity, Seizures, Hydrocephalus, Abnormal EEG, Demyelination and Diffuse demyelinating neuropathy

AR




75

Leber Congenital Amaurosis 10 and Other CEP290-Related Ciliopathies

CEP290

Severe vision loss or blindness, Seizures, Nystagmus, Photophobia, High hyperopia, Keratoconus and Sluggish or absent pupillary responses


AR




76

Leber Congenital Amaurosis 13

RDH12

Early onset Retinal dystrophy, Intraretinal bone spicule pigmentation, Attenuation of retinal arterioles, Legal blindness in early adulthood and Preservation of central vision into later adulthood.

AR




77

Leber Congenital Amaurosis 8

CRB1

profound vision loss, nystagmus, severe retinal dysfunction, high hypermetropia, photodysphoria, oculodigital sign, keratoconus and cataracts

AR




78

Leber Congenital Amaurosis 2

RPE65

Hypoplastic cerebellar vermis, Mental retardation, Pigmentary retinopathy, Blindness, Central visual loss, Fundus atrophy, Cataract, Keratoconus, Photophobia, Eye poking and Reduced electroretinogram (ERG).


AR




79

Leukoencephalopathy with Vanishing White Matter

EIF2B5

Macrocephaly, Optic atrophy, Ovarian failure (females), Unsteady gait, Loss of coordination, Developmental regression, Gait difficulties, Hypotonia, Lethargy, Seizures, Spasticity, Memory loss, Dysarthria, Cognitive deficits Personality changes and Emotional lability.


AR




80

Limb-Girdle Muscular Dystrophy, Type 2A

CAPN3

Facial weakness, Contractures, Symmetrical, proximal limb muscle atrophy, Difficulty walking, Motor clumsiness, Calf pseudohypertrophy (rare) and Transient eosinophilic myositis


AR




81

Limb-Girdle Muscular Dystrophy, Type 2B

DYSF

Proximal muscle weakness, Primarily affects lower limbs, Difficulty climbing stairs, Difficulty running, Increased fatigue, Muscle biopsy shows dystrophic changes, Muscle fiber splitting, Necrotic changes and Amyloid deposition in muscle fibers.

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

82

Limb-Girdle Muscular Dystrophy, Type 2C

SGCG

Right ventricular hypertrophy, Right ventricular dilatation, Restrictive lung disease, Pneumonia, Hyperlordosis, Scoliosis, Joint contractures, Muscle atrophy, Calf muscle pseudohypertrophy, Unstable gait, Gowers sign, Muscle fiber necrosis and Increased serum creatine kinase.

AR




83

Limb-Girdle Muscular Dystrophy, Type 2D

SGCA

Contractures, Cardiomyopathy (rare), Calf muscle hypertrophy, Necrosis and degeneration seen on muscle biopsy, Myopathic changes seen on EMG, Loss of reflexes due to myopathy and Increased serum creatine kinase.

AR




84

Limb-Girdle Muscular Dystrophy, Type 2E

SGCB

Scapular winging, Muscle weakness, Proximal muscle atrophy, Trunk muscle atrophy, Calf pseudohypertrophy, Increased serum creatine kinase and Dilated cardiomyopathy (rare).

AR




85

Limb-Girdle Muscular Dystrophy, Type 2I

FKRP

Tongue hypertrophy, Dilated cardiomyopathy, Left ventricular impairment, Nocturnal hypoventilation, Scoliosis, Spinal fusion, Lordosis, Kyphosis, Achilles tendon contractures, Waddling gait, Muscle cramps, Myalgia, Calf hypertrophy, Frequent fall and Increased serum creatine kinas.

AR




86

Lipoamide Dehydrogenase Deficiency

DLD

Microcephaly, Hypertrophic cardiomyopathy, Hepatomegaly, Liver dysfunction, Vomiting, Encephalopathy, Hypotonia, Delayed psychomotor development, Lethargy, Ataxia, Dystonia, Seizures, Metabolic acidosis and Leigh syndrome (in some patients).

AR




87

Lipoid Adrenal Hyperplasia

STAR

Hypospadias, Female phenotypic and Salt-wasting, Abnormal spermatogenesis, Abnormality of the menstrual cycle, Absence of secondary sex characteristics, Acidosis, Adrenocortical adenoma, Decreased fertility and Delayed skeletal maturation.

AR




88

Lipoprotein Lipase Deficiency

LPL

Lipemia retinalis, Bile duct stenosis, Nausea, vomiting, Splenomegaly, Hepatosplenomegaly, Episodic abdominal pain, Pancreatitis, Jaundice and Eruptive xanthomas.

AR




89

Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency

HADHA

Hypoketotic hypoglycemia, Photophobia, Abnormal electroretinogram, Exotropia, developmental delay, Hepatomegaly, Hypertrophic cardiomyopathy, Peripheral neuropathy, Visual loss, Hypoglycemia and Muscular hypotonia.

AR




90

Maple Syrup Urine Disease, Type 1a

BCKDHA

Pancreatitis, Vomiting, Feeding problems, Lethargy, Seizures, Ataxia, Coma, Mental retardation, Hypertonia, Hypotonia, Cerebral edema, Ketosis and Hypoglycemia.


AR




91

Maple Syrup Urine Disease, Type 1b

BCKDHB

AR




92

Meckel Syndrome 1

MKS1

Microcephaly, Sloping forehead, Micrognathia, Low-set ears, Microphthalmia, Hypotelorism, Hypertelorism, Iris coloboma, Cleft lip & palate, Macrostomia, Short webbed neck, Pulmonary hypoplasia, Asplenia, Omphalocele, Ambiguous genitalia, Syndactyly and Clinodactyly.

AR




93

Medium Chain Acyl-CoA Dehydrogenase Deficiency

ACADM

Hepatomegaly, Fatty infiltration of liver, Vomiting, Lethargy, Seizures, Coma, Cerebral edema, Developmental delay, Hypotonia, Hypoglycemia, metabolic acidosis and Acylglycinuria.

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

94

Megalencephalic Leukoencephalopathy with Subcortical Cysts

MLC1

Macrocephaly, Megalencephaly, Ataxia, Spasticity, Seizures, Delay in motor development, Mild mental retardation and Vacuolizing myelinopath.

AR




95

Menkes Disease

ATP7A

Short stature, Intrauterine growth retardation, Microcephaly, Brachycephaly, Wormian bones, Pudgy cheeks, Osteoporosis, Joint laxity, Hypopigmentation, Skin laxity, Neurologic degeneration, Hypotonia, Mental retardation, Seizures, Hypothermia and Intracranial hemorrhage.

XLR




96

Metachromatic Leukodystrophy

ARSA

Optic atrophy, Gallbladder dysfunction, Cholecystitis, Urinary incontinence, Loss of speech, Hypotonia, Hyporeflexia, Dystonia, Chorea, Ataxia, Spastic tetraplegia, Seizures, Bulbar palsies, Progressive polyneuropathy, Demyelination, Gait disturbances and Emotional lability.

AR




97

3-Methylcrotonyl-CoA Carboxylase Deficiency

MCCC1

Failure to thrive, Feeding difficulties, Apnea, Vomiting, Macro- and microvesicular steatosis, Hypotonia, Seizures, Lethargy, Coma, Hyperreflexia, Opisthotonus, Developmental delay, Mental retardation, Metabolic acidosis and Acute hypoglycemia.


AR




MCCC2

AR




98

3-Methylglutaconic Aciduria, Type III

OPA3

Optic atrophy, Decreased visual acuity, Ataxia, Spasticity, Hyperreflexia, Extrapyramidal signs, Choreiform movements, Cognitive defects and Dysarthria.

AR




99

Methylmalonic Acidemia

MUT

Failure to thrive, Cardiomyopathy, Hepatomegaly, Recurrent episodes of vomiting, Pancreatitis, Interstitial nephritis, Chronic renal failure, Lethargy, Hypotonia, Developmental delay, Coma, Delay in myelination, Cerebellar hemorrhage (rare), Dehydration, Leukopenia and Thrombocytopenia.


AR




100

Methylmalonic Acidemia

MMAA

Failure to thrive, Respiratory distress, Hepatomegaly, Vomiting, Lethargy, Hypotonia, Developmental delay, Coma, Dehydration, Ketosis, Pancytopenia, Neutropenia, Anemia, Thrombocytopenia, Ketonuria and Metabolic acidosis.


AR




MMAB

AR




101

Methylmalonic Aciduria and Homocystinuria, Cobalamin C Type

MMACHC

Failure to thrive, Microcephaly, Hydrocephalus, Long face, High forehead, Flat philtrum, Low-set ears, Pigmentary retinopathy, Nystagmus, Renal failure, Metabolic acidosis, Anemia, Neutropenia, Hypotonia, Lethargy, Developmental delay, Mental retardation, Seizures and Cortical atrophy.

AR




102

Mitochondrial Complex I Deficiency

NDUFAF5

Intrauterine growth restriction, Failure to thrive, Nystagmus, Ptosis, Optic atrophy, Global developmental delay, Neurologic regression, Spasticity, Choreoathetosis, Dystonic movements, Dysarthria, Seizures and Agenesis of the corpus callosum.


AR




103

Mucolipidosis II

GNPTAB

Progressive failure to thrive, Long philtrum, Coarse facial features, Thin eyebrows, Low nasal bridge, Macroglossia, Cardiomegaly, Scapular hypoplasia, Umbilical hernia, Hepatomegaly, Thickened cranium, kyphosis, Hip dislocation, Brachyphalangia, Cavernous hemangioma and Talipes.

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

104

Mucolipidosis IIIA

GNPTAB

Short stature, Corneal clouding, retinopathy, Hyperopic astigmatism, Aortic insufficiency, Scoliosis, Dysostosis multiplex, Scoliosis, Short long bones, Claw-hand deformities, Carpal tunnel syndrome, Absence of dens, Skin thickening, Learning disabilities and Mental retardation.

AR




105

Mucolipidosis IV

MCOLN1

Microcephaly, Corneal clouding, Optic atrophy, Photophobia, Strabismus, Achlorhydria, Hypotonia, neurologic deterioration, Spastic quadriplegia, Dystonia, Hyperreflexia, Mental retardation, Dysplastic corpus callosum, Dysmyelination of the brain and Cerebellar atrophy.

AR




106

Mucopolysaccharidosis, Type II

IDS

Scaphocephaly, Macrocephaly, Coarse facies, Hearing loss, otitis media, Papilledema, Retinal pigmentation, Ptosis, Macroglossia, Short neck, Asthma, hernia, Hepatosplenomegaly, Pebbly skin lesions, Kyphosis, Claw hand, Pes cavus, Hypertrichosis, Hydrocephalus, Cervical cord compression and Seizures

XLR




107

Mucopolysaccharidosis, Type IIIC

HGSNAT

Hearing loss, Synophrys, Retinitis pigmentosa, Fleshy nasal tip, Everted lower lip, Asymmetric septal hypertrophy, Thickened ribs, Diarrhea, Dysphagia, Dense calvaria, Dolichocephaly, Kyphoscoliosis, Synophrys, Hirsutism, Coarse hair, Mental retardation, Seizures and Temper tantrums.


AR




108

Mucopolysaccharidosis, Type IIID

GNS

Prominent forehead, Hearing loss, Low-set ears, Synophrys, Flat nasal bridge, Anteverted nares, Thick lips, Wide mouth, Drooling, Short neck, Thick ribs, Diarrhea, Dysphagia, Joint contractures, Hirsutism, Coarse hair, Thick eyebrows, Seizures, Dysarthria and Mental retardation.

AR




109

Mucopolysaccharidosis, Type IVb

GLB1

Prognathism, Hearing loss, Corneal opacities, Broad mouth, Widely spaced teeth, Grayish enamel, Restrictive lung disease, Prominent sternum, Inguinal hernia, Osteoporosis, Platyspondyly, Kyphosis, Hyperlordosis, Scoliosis, Coxa valga, Genu valgum, Coxa valga amd Joint laxity.

AR




110

Mucopolysaccharidosis, Type VI

ARSB

Macrocephaly, Hearing loss, Glaucoma, Corneal clouding, Low nasal bridge, Thickened lips, Macroglossia, Infantile cardiomyopathy, Broad ribs, hernia, Hepatosplenomegaly, Dysostosis multiplex, Hip dysplasia, Genu valgum, Mild hirsutism, Hydrocephalus and Carpal tunnel syndrome.


AR




111

Multiple Sulfatase Deficiency

SUMF1

Short stature, Large forehead, Prominent forehead, Periorbital edema, Flat face, Coarse facies, Deafness, Corneal clouding, Retinal degeneration, Upturned nose, Hepatosplenomegaly, Dysostosis multiplex, Broad thumbs, Ichthyosis, Mental retardation, Ataxia, Spasticity and Cerebral atrophy.

AR




112

Muscle-Eye-Brain Disease and Other POMGNT1-Related Congenital Muscular Dystrophy-Dystroglycanopathies

POMGNT1

Microcephaly, Midface hypoplasia, Mild micrognathia, Retinal dysplasia, Microphthalmia, Coloboma, Glaucoma, Cataracts, Chorioectopia, Optic nerve atrophy, Retinal hypoplasia, Buphthalmos, Megalocornea, Nystagmus, Strabismus, Hydrocephalus, Pachygyria, Seizures and Cerebellar cysts.

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

113

Nephrotic Syndrome / Congenital Finnish Nephrosis

NPHS1

Growth retardation, Proteinuria, Tubular atrophy, dilated proximal tubules, Mesangial cell proliferation, Diffuse mesangial sclerosis, Glomerulosclerosis, Interstitial fibrosis, Edema, Enlarged placenta, Prematurity, Hyperlipidemia and Hypoalbuminemia.

AR




114

Niemann-Pick Disease, Type A

SMPD1

Short stature, Cherry-red maculae, Hepatosplenomegaly, Diffuse reticular or finely nodular infiltrations, Protuberant abdomen, Neonatal jaundice, Vomiting, Osteoporosis, Xanthomas Hypotonia, Hyporeflexia, Mental retardation and Psychomotor retardation.

AR




115

Niemann-Pick Disease, Type B

116

Niemann-Pick Disease, Type C

NPC1

Respiratory failure, Hepatosplenomegaly, Dysphagia, Hypotonia, Developmental delay, Dysarthria, Loss of speech, Dementia, Spasticity, Dystonia, Seizures, Cerebellar ataxia, Cataplexy, Psychosis and Behavioral problems.


AR




NPC2

AR




117

Nijmegen Breakage Syndrome

NBN

Short stature, Microcephaly, Mastoiditis, Sloping forehead, Micrognathia, Large dysplastic ears, Otitis media, Choanal atresia, Long nose, Cleft lip, Cleft palate, Sinusitis, Bronchitis, Anal stenosis, Hydronephrosis, Cafe au lait spots, Depigmented spots, Rhabdomyosarcoma, Lymphoma and Glioma


AR




118

Non-Syndromic Hearing Loss

GJB2

Prelingual profound sensorineural hearing loss and Vestibular dysfunction.

AR




119

Omenn Syndrome

RAG2

Failure to thrive, Pneumonia, Hepatomegaly, Splenomegaly, Diarrhea, Generalized erythrodermia, Pachydermia, Alopecia, Anemia, Thrombocytopenia, Eosinophilia, Lymphadenopathy, Hypoproteinemia and Hypoplastic thymus.

AR




120

Omenn Syndrome / Severe Combined Immunodeficiency, Athabaskan-Type

DCLRE1C

Failure to thrive, Otitis media, Absent tonsils, Recurrent upper respiratory tract infections, Pneumonia, Diarrhea, Genital ulcers and Absent thymus

AR




121

Ornithine Transcarbomylase Deficiency

OTC

Failure to thrive, Protein avoidance, Vomiting, Lethargy, Episodic ataxia, Coma, Seizures, Cerebral edema, Developmental delay, Mental retardation, High ornithine, Hyperammonemia, Stroke(rare) and Irritability

XLR




122

Optic Atrophy 3, with Cataract

OPA3

Optic atrophy, Decreased visual acuity, Ataxia, Spasticity, Hyperreflexia, Extrapyramidal signs, Choreiform movements, Cognitive defects and Dysarthria.

AD




123

Pendred Syndrome

SLC26A4

Congenital neurosensory deafness, Vestibular function defect, Cochlear malformation, Goiter, Euthyroid and Hypothyroid

AR




124

Phenylalanine Hydroxylase Deficiency

PAH

Microcephaly, Blue eyes, Cataracts, Pale pigmentation, Dry skin, Eczema, Scleroderma, Blond hair, Mental retardation, Infantile irritability, Peculiar gait, Seizures, Brain calcification, Psychosis, Hyperactivity, Autistic features, Aggression, Self-mutilation, Depression and Anxiety disorder

AR




125

Pigmented Paravenous Chorioretinal Atrophy

CRB1

Pigmented paravenous chorioretinal atrophy,Bone corpuscle fundus pigmentation, Hyperopia, Esotropia,Vitreoretinal degeneration 

AD




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

126

Polycystic Kidney Disease, Autosomal Recessive

PKHD1

Potter facies, Hypertension, Lung hypoplasia, Periportal liver fibrosis, Portal hypertension, Hepatic cysts, Pancreatic cysts, Splenomegaly, Esophageal varices, Cystic kidneys, Renal failure, Interstitial fibrosis and Bile duct dilation and proliferation

AR




127

Primary Carnitine Deficiency

SLC22A5

Failure to thrive, Cardiomegaly, Hypertrophic cardiomyopathy, Congestive heart failure, Fatty infiltration of heart muscle, Hepatomegaly, Liver steatosis, Muscle weakness, Hypotonia, Lethargy, Encephalopathy, Coma associated with hypoglycemia and Reye syndrome.

AR




128

Primary Ciliary Dyskinesia


DNAI1

Chronic sinusitis, Conductive deafness, Chronic otitis media, Corneal abnormalities, Rhinitis, Nasal polyps, Anosmia, Dextrocardia, Bronchiectasis, Pneumonia, Situs inversus, Asplenia, Headaches, Infertility (male) and Immotile sperm (male).

AR




DNAH5

AR




129

Propionic Acidemia

PCCA

Short stature, Failure to thrive, Cardiomyopathy, Tachypnea, Apnea, Hepatomegaly, Pancreatitis, Vomiting, Dermatitis acidemica, Lethargy, Coma, Seizure, Cerebral atrophy, Dystonia, Metabolic acidosis, Pancytopenia, Neutropenia, Thrombocytopenia and Anemia

AR




130

Pyruvate Dehydrogenase E1-Beta Deficiency

PDHB

Low birth weight, Microcephaly, Narrow head, Frontal bossing, Long philtrum, Episodic ptosis, Wide nasal bridge, Upturned nose, Flared nostrils, Hypotonia, Lethargy, Psychomotor retardation, Mental retardation, Seizures, Choreoathetosis, Dystonia and Cerebral atrophy

AR




131

Pyruvate Dehydrogenase E1-Alpha Deficiency

PDHA1

XLR




132

6-Pyruvoyl-Tetrahydropterin Synthase Deficiency

PTS

Microcephaly, Oculogyric crises, Hypersalivation, Swallowing difficulties, Mental retardation, Hypotonia, Hyperreflexia, Ataxia, Tremor, Parkinsonism, Bradykinesia, Rigidity, Stiffness, Dystonia, Seizures, Somnolence, Episodic hyperthermia and Irritability

AR




133

Retinitis Pigmentosa 25

EYS

Night blindness, Photophobia, Retinal bone-spicule pigmentation, Attenuated retinal vessels, Constriction of visual field, Optic disc pallor, Chorioretinal atrophy (rare), Posterior subcapsular cataract (rare) and Nonrecordable ERG response (rare).

AR




134

Retinitis Pigmentosa 12

CRB1

Retinitis pigmentosa, Night blindness, Concentric visual field loss, Nystagmus, Attenuation of retinal arterioles and Bone spicule-type pigment deposits.

AR




135

Retinitis Pigmentosa 20

RPE65

Nystagmus, Night blindness, Severe visual impairment, Attenuated vessels of optic disc, Atrophy of optic disc, Whitish dots on ophthalmoscopy and Retinitis pigmentosa


AR




136

Smith-Lemli-Opitz Syndrome

DHCR7

Short stature, Microcephaly, Micrognathia, Low-set ears, Ptosis, Epicanthal folds, Cataracts, Hypertelorism, Strabismus, Cleft palate, Hypoplastic tongue, Dental crowding, Hypoplastic lungs, Vomiting, Pyloric stenosis, Hypospadias and Micropenis (male), Renal agenesis, Eczema and Neurologic signs

AR




Num.

Disease name

Gene

Phenotypic hallmarks

Inheritance

Severity

Mild

Moderate

Severe

137

Sulfate Transporter-Related Osteochondrodysplasia

SLC26A2

Fetal hydrops, Flat face, Short-limbed dwarfism, Respiratory insufficiency, Narrow chest, Thin short ribs, hernia, Distended abdomen, Small iliac bones, Severe micromelia, Metaphyseal spurring, Polyhydramnios and Breech presentation at birth

AR




138

Tay-Sachs Disease

HEXA

Cherry red spot, Blindness, Increased startle response, Hypotonia, Late hypertonia, Poor head control, Psychomotor degeneration, Seizures, Dementia and Apathy

AR




139

Tyrosinemia, Type I

FAH

Failure to thrive, Hypertrophic cardiomyopathy, Ascites, Hepatomegaly, Acute liver failure, Cirrhosis, Splenomegaly, GI bleeding, Paralytic ileus, Renal failure, Glomerulosclerosis, Nephromegaly, Nephrocalcinosis, Episodic paralysis and Rickets

AR




140

Usher Syndrome, Type IB

MYO7A

Absent vestibular function, Extinction of electroretinogram, Visual loss and Delayed motor development

AR




141

Usher Syndrome, Type ID

CDH23

Sensorineural hearing loss, Variable vestibular dysfunction, Retinitis pigmentosa, Nyctalopia, Progressive restriction of visual feilds and Reduction of central visual acuity

AR




142

Usher Syndrome, Type IF

PCDH15

AR




143

Usher Syndrome, Type IIA

USH2A

AR




144

Usher Syndrome, Type III

CLRN1

AR




145

Very Long Chain Acyl-CoA Dehydrogenase Deficiency

ACADVL

Hypertrophic cardiomyopathy, Cardiac arrest, Sudden cardiac death, Tachypnea, Hepatomegaly, Hepatic steatosis, Hepatocellular necrosis, Vomiting, Hypotonia, Muscle stiffness, Rhabdomyolysis with exercise, Lethargy and Nonketotic hypoglycemia

AR




146

Walker-Warburg Syndrome and Other FKTN-Related Dystrophies

FKTN

Optic atrophy, Retinal detachment, Strabismus, Myopia, Hyperopia, Cataracts, Microphthalmia, Retinal dysplasia, Myocardial fibrosis, Respiratory insufficiency, Progressive contractures, Spinal rigidity, Scoliosis, Muscular dystrophy, Hypotonia, Mental retardation, Polymicrogyria and Seizures

AR




147

Wilson Disease

ATP7B

Kayser-Fleischer ring, Hepatic cirrhosis, Hepatic coma, Hepatomegaly, Liver failure, Esophageal varices, Osteoporosis, Osteomalacia, Chondrocalcinosis, Osteoarthritis, Tremor, Dysarthria, Dysphagia, Dementia, Dystonia, Drooling and Poor motor coordination

AR




148

X-Linked Severe Combined Immunodeficiency

IL2RG

Failure to thrive, Oral thrush, Pneumonia, Hepatomegaly, Chronic diarrhea, Candidal diaper rash, Erythematous skin rashes, Recurrent bacterial meningitis and Agammaglobulinemia

XLR




149

Zellweger Syndrome Spectrum

PEX1

Failure to thrive, Flat occiput, Turribrachycephaly, Macrocephaly, Flat face, Round face, Micrognathia, High forehead, Hypertelorism, Cataracts, Brushfield spots, High arched palate, Metatarsus adductus, Talipes, Protruding tongue, Hypospadias (male) and Clitoromegaly (female).

AR




PEX2

High forehead, Micrognathia, Flat face, Low set ears, Cleft palate, Congenital heart defect, Hepatomegaly, Splenomegaly, Jaundice, Camptodactyly, Cubitus valgus, Cryptorchidism (male).

AR








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