GM26590
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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Italian
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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 |
5.64 |
| Passage Frozen |
8 |
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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 |
610661.0003; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
c.1370dupG, R458FsTER; In an Italian girl with congenital disorder of deglycosylation (CDDG; 615273), Enns et al. (2014) identified a homozygous 1-bp duplication (c.1370dupG) in exon 9 of the NGLY1 gene, resulting in a frameshift and premature termination (Arg458fsTer). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the Exome Variant Server database. |
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| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 2 |
610661.0003; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
c.1370dupG, R458FsTER; In an Italian girl with congenital disorder of deglycosylation (CDDG; 615273), Enns et al. (2014) identified a homozygous 1-bp duplication (c.1370dupG) in exon 9 of the NGLY1 gene, resulting in a frameshift and premature termination (Arg458fsTer). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the Exome Variant Server database. |
| Remarks |
Clinically affected; diagnosed at age 20; symptom onset at 4 months; poor growth in utero; repetitive, unilateral fetal movements; urinary tract infection during 3rd trimester of pregnancy; no known maternal exposures to teratogens; C-section; placenta noted to look old; abnormal birth weight and length despite 39 week gestation; exotropia; cafe au lait spot; global developmental delay; delayed fine motor development; severe intellectual disability; knows approximately 10 words and signs; hypotonia; ataxia; movement disorder; can stand and walk with support; absent reflexes; dystonia and chorea; peripheral neuropathy; cerebellar hypoplasia; ventriculomegaly; enlarged cisterna magna; cerebral cortical atrophy; enlarged pituitary gland; scoliosis; osteoporosis with history of fractures; recent increase in fractures; osteopenia; visual impairment; dry eyes; myopia; astigmatism; ocular apraxia; conjunctiva inflamed; dysconjugate gaze; corneal scarring; blepharitis; abnormality of optic nerve; hypolacrima; increased intraocular pressure; history of ezcema; previously unable to sweat, able to sweat as of 2013; reactive airway disease; sinus tachycardia; low blood pressure; constipation; moderate obstructive sleep apnea with mild desaturations; unspecified testing by neurologist showed significantly elevated transaminases up to 1200 and microcephaly; sural nerve biopsy; overnight EEG; whole exome sequencing identified homozygous mutation (c.1370dupG) in exon 9 of NGLY1 gene which results in p.R458fs; heterozygous carrier for mutation (c.175C>T) in exon 3 of GNE gene; requires breathing support when sedated due to underlying hypotonia; sweat test indicated absent sweat response in legs but normal response in forearms; EMG/nerve conduction study showed severe axonal sensorimotor neuropathy with motor nerves more severely affected than sensory nerves; brain MRI indicated small cerebellum; MRS indicated NAA levels low in cerebellum and pons, small upper cervical spinal cord; cerebral spinal fluid lab tests showed low albumin, IgG, and CSF protein at 9 mg/dL (15-45 mg/dL normal range); elevated blood lactate levels at 4 months were 3.9 mmol/l and at 1 year were 2.7 mmol/l (normal <2.2 mmol/l); OAE showed grossly abnormal ABR, suggesting auditory signal at brainstem is dyssynchronous; abdomin ultrasound showed inhomogeneous texture of liver suggesting diffuse liver disease; urine amino acids detected pattern of marked generalized amino aciduria indicative of renal tubulopathy; palmidronate therapy; atenolol 18 mg daily; restasis 0.05% 1 drop daily; refresh cream 1 strip in both eyes daily; vitamin D3 3,000 units twice daily; calcium acetate 500 mg once daily; has not received shingles vaccine; occupational, physical, and speech therapy; uses bilateral AFOs and a wheelchair; unaffected mother (GM25390) and father (GM25391) also in repository; for B-lymphocyte from same subject, see GM25389. [see Patient 2 in publication by Enns et al. 2014 - PMID 24651605]
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| Passage Frozen |
8 |
| Split Ratio |
1:2 |
| 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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