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 |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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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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DNA from LCL
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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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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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| 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; abnormal placenta; 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 fibroblast from same subject, see GM26590. [see Patient 2 in publication by Enns et al. 2014 - PMID 24651605]
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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 |
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