GM26584
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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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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Y
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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 |
5.8 |
| 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 16 years old; symptoms onset at birth; mother's heart rate decreased one week before birth resulting in emergency C-section at 37 weeks gestation; decreased movement noticed by mother 2 days before birth; nuchal cord; blue in color; severe hypoxia and resuscitation; admitted to the NICU for 24 hours due to low birth weight (4 pounds 7 ounces) and small birth length; experienced projectile vomiting and was diagnosed with anal stenosis within first month of life; very high, narrow palate; crowded teeth; dry lips; kyphosis; lagopthalmos; anteverted nares; abnormal face shape; at 6 weeks parents noticed she was not smiling and seemed hypotonic; at 6 months she was not rolling or sitting, diagnosed with developmental delay; began having involuntary movements around 6-12 months which gradually worsened; seizures started at age 10 or 11 and have worsened over time; atonic seizures; failure to thrive; GERD; severe constipation; incontinence; severe scoliosis; diffuse osteopenia; fatigues easily; amennorhea; microcephaly; deep reflexes hypoactive; non-verbal; severe intellectual disability; sensorimotor neuropathy; decreased sweating due to autonomic dysfunction; central sleep apnea; corneal clouding; hypolacrima with severe corneal scarring; corneal neovascularization; alacrima; optic nerve pallor; pigmentary retinal degeneration; blurred vision; dry eyes, no tears; very dry skin; deafness; severe otitis media; movement disorder; hyperkinesis; motor tone decreased in trunk and increased extensor tone in extremities; non-ambulatory; choreiform movements; dysmetria; tachycardia, heart rate 118 at rest; respiratory rate is 20 breaths per minute; elevated hepatic transaminases; slightly low prealbumin level at 17 mg/dL; TSH slightly elevated 5.19 mclU/mL; underweight; BMI 14.3; head circumference 52 cm; delayed fine and gross motor skills; exaggerated cellular immune processes; cranial nerve exam found poor oral muscle tone, hyperactive gag, upper and low face is weak; QSWEAT found abnormal sweat response in a length-dependent manner suggesting that it is related to a peripheral neuropathy rather than a generalized process; EMG/nerve conduction study found electrophysiological evidence of a combined axonal and demyelinating sensorimotor polyneuropathy, EMG showed abnormalities in all muslces tested: right arm, biceps, leg, vastus medialis, medical head of gastrocnemius; MRI/MRS found deficit of NAA in all four locations studied, deficit most pronounced in left centrum semiovale, this location also demonstrates an excess of choline, paranasal sinus inflammation includes mucosal thickening and mucus retention cysts; genetic testing revealed homozygous mutation (c.1201A>T) in NGLY1 gene resulting in p.R401X; neuro imaging showed abnormality of the cerebral cortex, cerebral cortical atrophy, abnormal metabolic brain imaging, reduced brain N-acetyl aspartate levels, and elevated brain choline levels; back brace for scoliosis; Botox tx and casting of legs as child for tight heel cords; medications include Keppra 500 mg IV twice a day, Miralax 17 gm PO daily in AM; artificial tears eye drops PRN 3-4 times a day; physical and occupational therapy from age 6 months to 6 years; G-tube considered due to rapid weight loss and difficulty swallowing; wheelchair; hearing aids did not help, deafness suspected to be neurological; affected sibling (GM26585 B-lymphocyte, GM26586 fibroblast), unaffected mother (GM26587 B-lymphocyte), and unaffected father (GM26588 B-lymphocyte) also in repository. |
| Passage Frozen |
4 |
| Split Ratio |
1:5 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| 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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