Description:
CHARCOT-MARIE-TOOTH DISEASE, TYPE 4C; CMT4C
DIASTROPHIC DYSPLASIA; DTD
SH3 DOMAIN AND TETRATRICOPEPTIDE REPEAT DOMAIN 2; SH3TC2
SOLUTE CARRIER FAMILY 26 (SULFATE TRANSPORTER), MEMBER 2; SLC26A2
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
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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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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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Old Order Mennonite
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Country of Origin
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USA
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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 |
5.91 |
| Passage Frozen |
2 |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
| |
| Gene |
SLC26A2 |
| Chromosomal Location |
5q32 |
| Allelic Variant 1 |
p.R279W; Diastrophic dysplasia |
| Identified Mutation |
p.R279W |
| |
| Gene |
SH3TC2 |
| Chromosomal Location |
5q32 |
| Allelic Variant 1 |
p.R954X; Charcot-Marie-Tooth disease, type 4C |
| Identified Mutation |
p.R954X |
| Remarks |
Clinically affected; oligohydramnios; fetal abnormalities noted on ultrasound: shortened long bones, club feet; born term by caesarian section due to suspicion of osteogenesis imperfecta; broad face and nose; cleft palate; mild 'cauliflower' changes of ear cartilage; severe and characteristic kyphoscoliosis= 40 degree rightward curvature thoracic, 30 degree leftward curvature lumbar, 40 degree lumbar lordosis; scoliosis; chest wall is rotationally distorted from clavicle to 12th rib; skeletal dysplasia (short stature); proportionately foreshortened limbs; short, campylodactic fingers; broad thumbs; brachydactyly (toes); genu valgum; talipes equinovalgus (club foot); clubbed toes; significant and symmetric hand weakness (grip strength 2/5) with arm positioning to compensate for weakness, most severe for extensor movements; less evident weakness of lower legs but absent deep tendon reflexes throughout; small atrial septal defect; recurrent pulmonary infection and respiratory insufficiency; gross motor development delayed: sat at 8 months, walked alone at 23 months; cognitive, language, emotional and social development are age-appropriate; exome sequencing revealed novel recessive digenic neuroskeletal disorder caused by pathogenic mutations in two genes: SLC26A2 (diastrophic dysplasia) and SH3CT2 (Charcot-Marie-Tooth type 4C demyelinating peripheral motor-sensory neuropathy) in linkage disequilibrium on chromosome 5; predominant expression of SH3CT2 on plasma membrane and perinuclear endosomes of Schwann cells, also found in spinal cord; surgeries: cleft palate successfully repaired; treated in parallel with myringotomies for two otitis medias with no recurrence; medications: albuterol sulfate, Qvar; family history: brother (not in repository) is also affected with CMT4C and diastrophic dysplasia and has inherited the same gene mutations. |
| Cumulative PDL at Freeze |
5.91 |
| Passage Frozen |
2 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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