GM26598
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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Scottish/English/American Indian
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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 |
5.1 |
| Passage Frozen |
3 |
| |
| 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 |
p.S116X; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
c.347C>G |
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| Gene |
NGLY1 |
| Chromosomal Location |
3p24.2 |
| Allelic Variant 2 |
IVS5+5G>T; CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG |
| Identified Mutation |
c.881+5G>T |
| Remarks |
Clinically affected; diagnosed at age 15; symptoms onset at birth; conception after low dose clomid therapy twice monthly; initial ultrasound at 11-12 weeks gestation noted twin gestation, but repeat ultrasounds triggered by pain at 28 weeks noted only 1 fetus; mother experienced significant nausea and vomiting during pregnancy; mother ran into electric fence during pregnancy; normal fetal movement; birth weight: 2722g (10th centile); length: 51 cm (75th centile) and OFC: 35.2 cm (70th centile) at day of life 6; presented day of life 4 with hypotonia, poor feeding, dehydration, jaundice, and elevated alkaline phosphatase of 293 IU,GGT of 802 IU (70-295),ALT 51 (6-50 IU/L), AST 56 (10-60 IU/L) ; at age 2 weeks ALT rose to 201 and AST to 236; at 10 weeks ALT was 200 and AST 236; did not feed well immediately after birth; osteopathic physician realigned overriding skull sutures, patient began eating better after this procedure; esotropia; lagophthalmous; plagiocephaly; anisocoria; hypotonia; dystonia; choreiform movements; delayed skeletal maturation; skeletal muscle atrophy; severe developmental delay; severe intellectual disability; microcephaly; cerebellar atrophy; no pincer grasp; deep reflexes hypoactive; non-verbal; seizure disorder; seizures began at age 10 with eyelid fluttering, eye deviation, and perioral cyanosis; severe axonal sensorimotor polyneuropathy with associated muscle wasting; erythematous perifollicular hyperkeratotic papules on all extremities; cyanosis below eyes and lips; constipation; malnutrition with low vitamin D levels; history of hepatomegaly; severe scoliosis; right hip subluxed; diffuse osteopenia; right femur and humerus dislocation; osteoporosis; somatic dysfunction of skull, membranous articular strain of the dura of the skull; reduced bone mineral density; bilateral coxa valga; takes very long time to wake up from anesthesia; transaminase levels elevated to the 300s; elevated serum creatine phosphokinase; increased resting energy expenditure; exaggerated cellular immune response; loss of sweat function in the distal leg limb, suggesting a length-dependent small fiber neuropathy; blink apraxia; exposure keratitis; inferior corneal thickening and inflammation; alacrima; neovascularization; ptosis; no synchronous activity though 8th cranial nerve; cannot recognize speech but can recognize the presence of sounds; dental enamel slightly different from others; bruxism; liver biopsy noted cirrhosis, yet was normalized by age 6-7; EMG/NCS noted severe axonal sensorimotor poly neuropathy, motor nerves may be slightly more affected than sensory; EEG found mild to moderate cerebral dysfunction; MRS found reduced brain N-acetyl aspartate levels and elevated brain choline levels; urine oligosaccharide analysis showed prominent species at m/z=991, a finding seen frequently in NGLY1-CDG individuals; exome sequencing (UCSC hg19) of the NGLY1 gene revealed that the donor is a compound heterozygote for the following mutations: maternally inherited c.347C>G (p.S116X) in exon 3 and paternally inherited c.881+5G>T (IVS5+5G>T) in intron 5, predicted to abolish the splice donor site of exon 5 causing abnormal gene splicing; donor subject is also heterozygous for the p.G531R mutation in the MYBPC3 gene associated with hypertrophic cardiomyopathy; rod placement in lower back due to scoliosis; pseudomonas wound infection from spinal fusion surgery; uses computer dinavox to communicate; scleral injections in both eyes; strabismus surgery at age 3; physical, occupational, and speech therapy; used nebulized albuterol and pulmicort after repeated bronchitis; keppra 1250 mg twice daily, miralax 17 g daily in AM, glycerin 1.5 g per rectum as needed, refresh PM 0.5 inch ribbon to both eyes once daily at bedtime, refresh eye drops 1-2 drops to both eyes as needed and daily; maternal aunt’s son has cerebral palsy; mother (GM25597 B-lymphocyte; GM26599 fibroblast) and father (GM25598 B-lymphocyte; GM26600 fibroblast) also in repository; see GM25596 for B-lymphocyte; [Clinical information from publication by J. Heeley and M. Shinawi 2014 – PMID 25707956]. |
| Heeley J, Shinawi M, Multi-systemic involvement in NGLY1-related disorder caused by two novel mutations American journal of medical genetics Part A167A:816-20 2014 |
| PubMed ID: 25707956 |
| Passage Frozen |
3 |
| Split Ratio |
1:3 |
| 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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