GM25347
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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Not Hispanic/Latino
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Ethnicity
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German
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Country of Origin
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GERMANY
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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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Confirmation
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Molecular characterization before cell line submission to CCR
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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 |
610661.0002; 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. |
| |
| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 2 |
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; diagnosed by geneticist at 2 years of age; onset of symptoms at birth; delivered by Cesarean section at 38 weeks gestation when fetal distress was noted on cardiotocography; intrauterine growth restriction; neonatal jaundice; hypotonia; constipation in infancy; intermittent head flexion at 6 months; global developmental delay; movement disorder; involuntary movements of upper extremities noted at 8 months; seizures - mild myoclonic seizures with head and body flexion occurred and evolved to single, symmetric spasms with bilateral arm extension shortly after 8 months; abnormal sleep patterns characterized by paucity of deep sleep and frequent awakenings; alacrima (abnormal tear production); unilateral ptosis; recurrent episodes of keratoconjunctivitis and poor lid closure during sleep; corneal ulcerations/scarring; chalazions; strabismus; decreased deep tendon reflexes; liver fibrosis; scoliosis; small hands and feet; donor subject learned to crawl and communicate with vocalizations; auditory brainstem response hearing abnormalities detected; electroencephalography (EEG) at 8 months showed generalized polyspike discharges; brain imaging (MRI) at various ages revealed: delayed myelination at 6 months, delayed myelination and supratentorial atrophy secondary to steroid therapy at 10 months, delayed myelination and recovery from supratentorial atrophy at 19 months; elevated blood lactate; elevated liver transaminases (three to four times upper limit of normal) noted in infancy; elevated alpha-fetoprotein; genetic testing revealed homozygous recessive nonsense mutation in NGLY1 gene: c.1201A>T (p.R401X) - found on both the maternal and paternal alleles by Sanger sequencing; management: physical therapy, occupational therapy, speech language therapy; medications: Lamictal, Depakote; epilepsy has been intractable despite many therapeutic trials; described as patient 4 by Enns et al 2014 (PMID 24651605); unaffected carrier mother is GM25348 (lymphoblast). |
| 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 |
| Split Ratio |
1:4 |
| 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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