GM20950
Fibroblast from Skin, Unspecified
Description:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id
ALG3, S. CEREVISIAE, HOMOLOG OF; ALG3
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
Fibroblast from Skin, Unspecified
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
| |
| Gene |
ALG3 |
| Chromosomal Location |
3q27 |
| Allelic Variant 1 |
R171Q; CONGENITAL DISORDER OF GYLCOSYLATION, TYPE Id |
| Identified Mutation |
ARG171GLN |
| |
| Gene |
ALG3 |
| Chromosomal Location |
3q27 |
| Allelic Variant 2 |
R171Q; CONGENITAL DISORDER OF GYLCOSYLATION, TYPE Id |
| Identified Mutation |
ARG171GLN |
| Remarks |
Clinically affected; born at 36 weeks gestation; at 29-31 weeks gestation, ultrasound and MRI diagnosed the following abnormalities: shortened femurs (5th centile), complete agenesis of the corpus callosum, Dandy-Walker malformation with dilated fourth ventricle, absent cerebellar vermis with small cerebellar hemispheres, enlarged cisterna magna, posterior fossa cyst, bilateral hydronephrosis and hydroureters, bilaterally flexed wrists and fingers, and oligohydramnios; normal prenatal karyotype; birth weight = 3.25 kg (25-50%); birth length = 50.0 cm (50%); birth head circumference = 31 cm (<3%); thickened, large, low-set ears with abnormally shaped pinnae; unilateral posterior ear creases; flatened nasal bridge; thin upper lip; micrognathia; shortening of all extremities; fingers and toes were long and thin with flexion contractures of wrists, knees, and fingers; overlapping toes on one foot; inverted, widely spaced nipples; abnormal fat distribution in buttocks and anterior and posterior neck; large, irregularly shaped hemangioma over buttocks and posterior right leg; weak cry and poor suck; lethargic; severe hypotonia; bilateral optic nerve atrophy with poorly reactive pupils; radiological exam showed short vertebral bodies, short ribs, short radii and ulnae, short femurs, tibiae and fibulae, paddle-shaped iliac wings, and bilateral small scapulae; sacral agenesis; widening of spinal canal; severe biventricular thickening; small atrial septal defect; recurrent hypoglycemia (less than 2.2 mmol/liter); hyperinsulinemia present during hypoglycemic episodes; suppressed beta-hydroxybutyrate (0.02 mmol/liter, reference 0.06-0.17); thrombocytopenia; elevated creatine kinase (662-1,483 U/liter); mildly elevated transaminases with AST of 55-283 U/liter; diminished liver synthetic function with total protein of 3.5 g/dl, albumin of 1.7 g/dl, and prolonged coagulation with a prothrombin time of 22.1 sec and partial thromboplastin time of 79 sec; died of urosepsis at 19 days of life; postmortem exam showed lungs with incomplete lobation bilaterally, hypertrophied cardiac ventricles, large liver with several well-defined lobular structures protruding from anterior surface, cut hepatic surface contained dilated bile lakes, spleen contained fissure along entire length, and reproductive system contained double-barrel vagina and bi-cornuate uterus; islet cell hyperplasia with increased beta-cell mass; carbohydrate-deficient transferrin analysis by electrospray ionization-mass spectrometry showed a ratio of transferrin molecules carrying one sugar chain/two sugar chains of 0.437 (normal <0.074) whereas ratio of nonglycosylated transferrin to those with two sugar chains was normal; normal activity of phosphomannomutase and phosphomannose isomerase; fibroblasts found to accumulate the truncated LLO species Man5GlcNAc2-P-P-Dol; donor subject is homozygous for a G>A transition at nucleotide 512 of the ALG3 gene [512G>A] resulting in a substitution of glutamine for arginine at codon 171 [Arg171Gln (R171Q)].
|
| Sun L, Eklund EA, Chung WK, Wang C, Cohen J, Freeze HH, Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia The Journal of clinical endocrinology and metabolism90:4371-5 2005 |
| PubMed ID: 15840742 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
10% |
| Percent O2 |
AMBIENT |
| Medium |
Dulbecco Modified Eagles Medium (high glucose) with 2mM L-glutamine or equivalent |
| Serum |
10% fetal bovine serum Not inactivated |
| Supplement |
- |
|