GM25340
LCL from B-Lymphocyte
Description:
CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG
N-GLYCANASE 1; NGLY1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
PIGI Consented Sample |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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LCL from B-Lymphocyte
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Race
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White
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Ethnicity
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Hispanic/Latino
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Ethnicity
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Puerto Rican/German/Polish
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Country of Origin
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USA
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Family Member
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1
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Family History
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N
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Relation to Proband
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proband
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 1 |
610661.0001; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
c.1891delC |
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| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 1 |
610661.0002; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
ARG401TER; For discussion of the arg401-to-ter (R401X) mutation in the NGLY1 gene that was found in compound heterozygous state in a patient with congenital disorder of deglycosylation (CDDG; 615273) by Need et al. (2012), see 610661.0001. |
| Remarks |
Clinically affected; onset of symptoms at birth; diagnosed with N-glycanase deficiency at 4 years of age; symptoms at birth: neonatal jaundice, global developmental delay, hypotonia, involuntary movements (athetosis involving the trunk and extremities and constant lip smacking and pursing), intractable multifocal epilepsy (consisting of myoclonic seizures, drop attacks, and staring or tonic episodes), abnormal liver function; At 15 months of age subject showed regression of motor development; At 4 years of age subject was noted to have cortical vision impairment, congenital alacrima (absence of tears), corneal ulcerations with scarring; At 5 years of age subject continues to have movement disorder, able to sit up, able to reach for objects and transfer them from hand to hand, never developed speech, abnormal EEG, decreased deep tendon reflexes, seizures, chalazions, elevated liver transaminases, elevated AFP, liver fibrosis, liver storage or vacuolization, constipation, peripheral neuropathy, small hands and feet; brain MRI at 8 months was normal but brain MRI at 15 months detected prominent perivascular spaces with surrounding gliosis in periatrial white matter and mildly delayed myelination; liver biopsy showed inflammatory changes with an amorphous substance in the cytoplasm; abnormal urine oligosaccharides with keratan sulfate, heparan sulfate, and chondroitin sulfate; testing for congenital disorders of glycosylation was normal by transferrin isoelectric focusing and N-glycan analysis; biochemical testing by Western blot showed no detectable NGLY1; molecular genetic testing by whole exome sequencing (WES) revealed compound heterozygous mutations in the NGLY1 gene: maternally inherited c.1891delC (p.Q631fs - frameshift mutation in exon 12) and paternally inherited c.1201A>T (p.R401X - nonsense mutation in exon 8); treatment and management includes: medications, physical therapy, occupational therapy, and speech language therapy; assistive devices: wheelchair, braces, orthotics, communication/learning device; mother (GM25341); father (GM25342) . [Subject is referenced as Trio 2 in publication by Needs et al 2012 – PMID 22581936, and Patient 1 in publication by Enns et al. 2014 - PMID 24651605] |
| Sarute N, Ross SR, CACNA1S haploinsufficiency confers resistance to New World arenavirus infection Proceedings of the National Academy of Sciences of the United States of America117:19497-19506 2020 |
| PubMed ID: 32719120 |
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| Enns GM, Shashi V, Bainbridge M, Gambello MJ, Zahir FR, Bast T, Crimian R, Schoch K, Platt J, Cox R, Bernstein JA, Scavina M, Walter RS, Bibb A, Jones M, Hegde M, Graham BH, Need AC, Oviedo A, Schaaf CP, Boyle S, Butte AJ, Chen R, Clark MJ, Haraksingh R, Cowan TM, He P, Langlois S, Zoghbi HY, Snyder M, Gibbs RA, Freeze HH, Goldstein DB, Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway Genetics in medicine : official journal of the American College of Medical Genetics16:751-8 2013 |
| PubMed ID: 24651605 |
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| Need AC, Shashi V, Hitomi Y, Schoch K, Shianna KV, McDonald MT, Meisler MH, Goldstein DB, Clinical application of exome sequencing in undiagnosed genetic conditions Journal of medical genetics49:353-61 2012 |
| PubMed ID: 22581936 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
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