GM25990
Fibroblast from Skin, Skin
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 |
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Biopsy Source
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Skin
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Skin
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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/Irish/Scottish/Swedish/Dutch/Italian
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Country of Origin
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USA
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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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| PDL at Freeze |
2.17 |
| Passage Frozen |
2 |
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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 |
610661.0004; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
3-BP DEL, 1205 TTC; In a 4-year-old Caucasian girl of European descent with congenital disorder of deglycosylation (CDDG; 615273), Enns et al. (2014) identified compound heterozygosity for 2 mutations in the NGLY1 gene: a 3-bp deletion (c.1205_1207delTTC), resulting in the deletion of 1 residue (402del), and a c.1570C-T transition, resulting in an arg542-to-ter (R542X; 610661.0005) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. |
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| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 2 |
610661.0005; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
ARG542TER, c.1570C>T; For discussion of the arg542-to-ter (R542X) mutation in the NGLY1 gene that was found in compound heterozygous state in a patient with congenital disorder of deglycosylation (CDDG; 615273) by Enns et al. (2014), see 610661.0004. |
| Remarks |
Clinically affected; diagnosed at 3 years 4 months of age; onset of symptoms from birth; 2nd trimester pregnancy positive screen for Smith-Lemli-Opitz syndrome and trisomy 18: alpha-fetoprotein (AFP) 1.63 multiple of the median (MoM), unconjugated estriol (uE3) 0.26 MoM, human chorionic gonadotrophin 0.54 MoM, inhibin 1.02 MoM, amniocentesis karyotype was normal; born by Cesarean section at term due to concerning fetal heart tracing; monitored in NICU due to poor feeding and lethargy; neonatal period: hyperbilirubinemia treated with phototherapy; elevated liver transaminases and transient thrombocytopenia, in infancy: global developmental delay, acquired macrocephaly, bilateral exotropia, hypotonia, constipation, at 1 year: no tears while crying, but enough to keep eyes moist, once-daily staring spells for about 15 seconds each, at 17 months: developed extrapyramidal movement disorder with asynchronous myoclonic jerks of the limbs and shoulders and subtle choreoathetotic movements of the hands and fingers; 4 years of age: ambulated unassisted with unsteady gait, communicated with use of vocalizations, gestures, and an assistive communication device; donor subject noted to have: small hands/feet; chalazions; strabismus; ocular apraxia; auditory brainstem response abnormalities; elevated blood lactate levels (3.7-7.5 mmol/l in infancy, 6.4 mmol/l at 21 months, 6.7 mmol/l at 31 months, 3.7 mmol/l at 32 months); liver storage or vacuolization; MRI results: mild global reduction in cerebral hemisphere volume and thin corpus callosum and anterior commissure noted in MRI at 17 months, MRS normal; whole genome sequencing (Sanger, Next-Generation Sequencing, hg19) performed at two different institutions revealed the donor subject is compound heterozygous for two mutations in the NGLY1 gene: a 3-base pair in-frame TTC> deletion beginning at position 3:25775416 (c.1205_1207del, p.402del) also identified in the proband’s mother (not in repository) and a stop-gain mutation at position 3:25761670 (c.1570C>T, p.R542X) also identified in proband’s father (not in repository); medications/supplements: N-acetylcysteine, Periactin, Miralax, Cocoavia, Theratears eye drops, Refresh PM ointment, children's probiotic, Albuterol inhaler; management: physical therapy, occupational therapy, and speech language therapy; assistive devices: orthotics and communication/learning device. [Donor subject is referenced as Patient 3 in publication by Enns et al. 2014 - PMID 24651605.] |
| Lin VJT, Hu J, Zolekar A, Salick MR, Mittal P, Bird JT, Hoffmann P, Kaykas A, Byrum SD, Wang YC, Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids Cell death & disease13:262 2022 |
| PubMed ID: 35322011 |
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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 |
| Cumulative PDL at Freeze |
5.68 |
| Passage Frozen |
2 |
| Split Ratio |
1:5 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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