GM26607
Fibroblast from Skin, Arm
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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Arm
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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, Arm
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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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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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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 |
4.37 |
| Passage Frozen |
4 |
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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. |
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| 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 at age 2; symptom onset at birth; pregnancy complicated by questionable history of fetal bradycardia on stress test; IUGR diagnosed at 34 weeks; began losing weight at 34 weeks as seen by ultrasound; fetal movement described as decreased, with frequent hiccups; born via LSCS; abnormal birth weight, length, and head circumference; abnormal face shape; strabismus; optic disk pallor; global developmental delay; delayed gross and fine motor development, with motor skills being the lowest score compared to other categories on Vineland Adaptive Behavior Scales; sat independently at 2 years 10 months; moderate intellectual disability; progressive myoclonic and atonic infantile epilepsy, which started at 2 months; at 11 months was having 200 myoclonic seizures per day; axonal sensorimotor polyneuropathy; demyelinative features; obstructive and central sleep apnea; hypotonia; hyperkinetic movement disorder; hypermobility of toe joints; reduced bone mineral density; abnormality of pelvic girdle bone morphology; coxa valga; chronic constipation; history of elevated hepatic transaminases (possibly from anti-seizure medication); increased serum lactate; slightly decreased creatine; slightly low insulin-like growth factor and serum insulin levels; decreased resting energy expenditure; hypolacrima; nocturnal lagophthalmos; corneal scarring; conjunctivitis; hypohidrosis; intermittent ptosis; bilateral inferior corneal pannus with old neovascularization; slight eustachian tube dysfunction present bilaterally; absence of otoacoustic emissions and tympanometry, supporting right middle ear dysfunction, hearing loss with a possible conductive origin cannot be ruled out; BMI 14.5 kg/M2; asthma; respiratory rate 20 breaths per minute; head circumference 50 cm; EMG/NCS testing was abnormal with sensory fibers more affected; MRI showed left posterior plagiocephaly, mild to moderate cerebral atrophy or volume loss with central pattern, mild variant of the Dandy-Walker malformation, possible atrophy of visual pathways, mucosal inflammation throughout paranasal sinuses, and deficit of NAA in the left centrum semiovale (cerebral white matter) and pons; sweat test showed absence of sweating in ankle and forearm; skeletal survey showed signs of osteopenia in feet; EEG showed multifocal sharp transients in the left frontal greater than left temporal and left occipital regions, likely epileptiform, although they were very short duration and at times appeared similar to muscle artifact in similar distributions; single gene sequencing to detect mutations in NGLY1 gene was done at GeneDX detected homozygous mutation (c.1201A>T) resulting in R401X; began taking valproate in 2014 and has been seizure free since and developmentally improved; physical, occupational, and speech therapy; medications include valproic acid 300 mg/400 mg twice daily (AM/PM), lamictal 25 mg twice daily, calcium 600 mg twice daily, vitamin D 1200 IE daily in AM, melatonin 3 mg at bedtime as needed for sleep; maternal twin aunt has cerebral palsy from birth injury; paternal aunt has dyslexia; unaffected mother (GM25348 B-lymphocyte; GM26608 fibroblast) and father (GM26609 B-lymphocyte; GM26610 fibroblast) also in repository; see GM25347 for B-lymphocyte. |
| 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 2021 |
| PubMed ID: 35322011 |
| Passage Frozen |
4 |
| Split Ratio |
1:6 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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