NA20949
DNA from Fibroblast
Description:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ic
ALG6, S. CEREVISIAE, HOMOLOG OF
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
|
Biopsy Source
|
Unspecified
|
|
Cell Type
|
Fibroblast
|
|
Tissue Type
|
Skin
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
DNA from Fibroblast
|
|
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 |
ALG6 |
| Chromosomal Location |
1p22.3 |
| Allelic Variant 1 |
delI299; CONGENITAL DISORDER OF GLYCOSYLATION; TYPE Ic |
| Identified Mutation |
897_899delAAT |
| |
| Gene |
ALG6 |
| Chromosomal Location |
1p22.3 |
| Allelic Variant 2 |
skipped ex 7-12 plus 22 bps of ex 13; CONGENITAL DISORDER OF GLYCOSYLATION; TYPE Ic |
| Identified Mutation |
IVS7+2T>G |
| Remarks |
Clinically affected; decreased fetal movements during pregnancy; birth weight = 3,500 g; spells of cyanosis and apnea during feeding in first 2 weeks of life; radiological evaluation showed bilateral reduction deformities of distal phalanges of digits II to IV in both hands and absence of the mid and distal phalanges on digits II to IV in the feet; right great toe has reduction of proximal phalanx and absence of distal phalanx; sat at 15 months, cruised at 3 years, walked independently at 5 years, first words at 5 years; 2 episodes of generalized epilepsy at age 20 months with normal EEG; grand mal seizures at ages 9 and 12 years; menarche at 15 years; irregular menses treated with medroxyprogesterone but followed by development of hirsutism; switched to triphasic contraceptive but excessive weight gain continued and male pattern frontal balding developed; pronounced virilization; deep vein thrombosis of left superficial femoral and deep popliteal vein developed at age 19 years; at 21 years, papilledema, as a result of pseudotumor cerebri, with normal venous MRI angiogram was noted; abdominal CT showed large ovaries with suspicion of multiple cysts; severe mental retardation; broad-based walk with kyphotic posture; normal muscle tone and deep tendon reflexes; dysmetria and intention tremor; distal phalangeal hypoplasia with small tapering nails, pointed distal digits, short distal phalanges and absent middle phalanx on the left second digit; normal brain MRI; abnormal coagulation factors: prothrombin time 11.4 sec (9.2-11.8), partial thromboplastin time 40.1 sec (20.6-32.9), antithrombin III 28 U/dl (88-131), Factor XI total 12.2 U/dl (52-120), protein C 24 U/dl (70-140), and protein S 42.2 U/dl (70-134); low LDL cholesterol of 44 mg/dl (62-136) but normal HDL cholesterol of 47 mg/dl (37-68); diagnosis confirmed using carbohydrate deficient transferrin analysis by electrospray ionization mass spectrometry; normal activities of phosphomannomutase, phosphomannose isomerase; donor subject is a compound heterozygote: one allele has a three base deletion in exon 9 of the ALG6 gene [897-899delAAT] that causes the loss of I299 and a second allele has an intronic mutation in intron 7 of the ALG6 gene [IVS7+2T>G] that disrupts splicing and causes skipping of exons 7-12 plus 22 bases of exon 13.
|
| Sun L, Eklund EA, Van Hove JL, Freeze HH, Thomas JA, Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient American journal of medical genetics Part A137:22-6 2005 |
| PubMed ID: 16007612 |
|