GM26612
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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British/English
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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 |
5.68 |
| Passage Frozen |
7 |
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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 15 years of age; symptom onset at birth; pregnancy complicated by maternal flare of Crohn's disease with low grade fevers requiring prednisone during second and third trimester; maternal migraines requiring Demerol and Gravol, and nausea; decreased fetal movement; born at 41 ½ week gestation via emergency C-section after induction followed by incomplete non-stress test with decreased fetal heart rate; abnormal weight, length, and head circumference; high respiratory rate immediately after birth respiratory rate; on exam, there was decreased air entry on the left, CXR confirmed pneumothorax on the left; seemed twitchy in first 48 hours of life, but physicians did not believe this was due to seizures; was stiff in the hips, knees, and ankles; within first few months of life, parents noticed persistent twitching, frequent crying, and chronic constipation; blepharitis; developmental delay; delayed fine and gross motor development; sitting at 9-10 months in a tripod position, creeping at 18 months, raking grasp at 13 months; able to use spoons and sippy cups; was able to climb stairs at age 3, but has been wheelchair bound since age 4; chokes on saliva; delayed speech and language development; moderate intellectual disability; progressive microcephaly; axonal neuropathy; staring episodes may be due to seizures, but it is not known if this is behavioral or epileptic; EEG normal; obstructive sleep apnea; length-dependent loss of sweat function, suggesting small fiber hyperkinetic movement disorder; muscular hypotonia; decreased strength; deep reflexes hypoactive; electrophysiological evidence of a severe axonal sensorimotor polyneuropathy; choreiform movements since birth; peripheral reflexes progressively decreased; scoliosis; small hands and feet; proximally placed thumbs; diffuse symmetric sclerosis of bilateral phalanges of the second, third, fourth, and fifth fingers; flexion deformity of bilateral second to the fifth fingers; bilateral pes planus; abnormality of the vertebral column, no definite abnormality identified; delayed skeletal maturation; reduced bone mineral density; BMI 14.6 kg/M2; head circumference 52 cm; keratoconus; hypo-lacrima; dry eyes; strabismus; ptosis; optic disk pallor; bilateral optic nerve pallor; corneal scarring; inflamed conjunctiva; constipation; recurrent bladder infections; sinus tachycardia; decreased resting energy expenditure; brain MRI at 13 months of age showed volume loss and white matter loss that was read to be consistent with ischemia; neurologist also noticed head circumference decreased from 10th percentile to 2nd percentile; ischemia was attributed to hypoxia at birth and diagnosed with cerebral palsy; MRI at age 16 showed left posterior plagiocephaly, small lesion in right frontal lobe (white matter unchanged), polyps and/or mucous retention cysts are present in maxillary sinuses (mild mucosal inflammation), variant vascular anatomy, deficit of NAA detected in left centrum semiovale and superior cerebellar vermis; neurological exam noted dysarticulate speech, skew up gaze, drooling, and poor oral muscle tone; mood swings; snores at night; wakes up at night and is sleepy during the day; liver specialist noted no transaminitis, but levels were elevated at birth; concentrations of several unrelated amino acids present in plasma; urine oligosaccharide and glycan screening showed prominent oligosaccharide species at m/z = 991; auditory brainstem response (ABR) absent bilaterally, representing significant dyssynchrony of auditory nerve and auditory brain stem tracts of each ear; genetic testing verified by sanger sequencing found homozygous mutation c.1201A>T (p.Arg401X) in the NGLY1 gene; orthopedic surgery; T3 and L5 posterior spinal fusion at 11 years; 4 salivary duct ligation for silorrhea and tarsorrhaphy surgery for lagophthalmos at 14 years; history of a blood transfusion; medications include lacrilube 0.5 inch ribbon to both eyes 3 times daily, Dulcolax per rectum as needed, and Fucidin as needed; allergic to sulfa drugs; speech, occupational and physical therapy; mother has Crohn's disease and history of speech delay until age 3; father is 6 feet 4 inches tall and has history of spontaneous pneumotharaces as a teenager, cardiac arrhythmias, keratoconus and has been partially worked up for Maranoid syndrome, but never diagnosed; maternal half-brother has ADHD and speech/sensory integration problems, delayed speech development, a stutter, and decreased reflexes in lower extremities; maternal grandfather with heart disease; maternal grandmother with lung fibrosis, CREST syndrome, and Raynaud's disease; paternal grandfather with lung cancer; maternal great-grandfather with epilepsy but without intellectual disability; no known consanguinity; unaffected mother (GM26613 B-lymphocyte; GM26614 fibroblast) and father (GM26615 B-lymphocyte; GM26616 fibroblast) also in repository; see GM26611 for B-lymphocyte.
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| Pavlinov I, Farkhondeh A, Yang S, Xu M, Cheng YS, Beers J, Zou J, Liu C, Might M, Rodems S, Baumgärtel K, Zheng W, Generation of two gene corrected human isogenic iPSC lines (NCATS-CL6104 and NCATS-CL6105) from a patient line (NCATS-CL6103) carrying a homozygous pR401X mutation in the NGLY1 gene using CRISPR/Cas9 Stem cell research56:102554 2021 |
| PubMed ID: 34619643 |
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| Yang S, Cheng YS, Li R, Pradhan M, Hong J, Beers J, Zou J, Liu C, Might M, Rodems S, Zheng W, An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous pR401X mutation in the NGLY1 gene Stem cell research39:101496 2019 |
| PubMed ID: 31326749 |
| Passage Frozen |
7 |
| Split Ratio |
1:4 |
| 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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