GM26611
LCL from B-Lymphocyte
Description:
CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG
N-GLYCANASE 1; NGLY1
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
PIGI Consented Sample |
|
Cell Type
|
B-Lymphocyte
|
|
Transformant
|
Epstein-Barr Virus
|
|
Sample Source
|
LCL from B-Lymphocyte
|
|
Race
|
White
|
|
Ethnicity
|
Not Hispanic/Latino
|
|
Ethnicity
|
British/English
|
|
Country of Origin
|
USA
|
|
Family Member
|
1
|
|
Family History
|
N
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Molecular characterization before cell line submission to CCR
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
| |
| 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. |
| |
| 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 GM26612 for fibroblast. |
| Split Ratio |
1:4 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
|