GM25447
Fibroblast from Skin, Skin
Description:
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 7; MDDGA7
ISOPRENOID SYNTHASE DOMAIN-CONTAINING PROTEIN; ISPD
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Muscular Dystrophies
CMD Specific
PIGI Consented Sample |
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Biopsy Source
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Skin
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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, Skin
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Race
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White
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Subject Type
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trio
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Ethnicity
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FRENCH-CANADIAN/SCOTTISH/IRISH
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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 |
3.68 |
| Passage Frozen |
10 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
CRPPA |
| Chromosomal Location |
7p21.2 |
| Allelic Variant 1 |
614631.0015; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 7; MDDGC7 |
| Identified Mutation |
c.1114_1116del(p.Val372del) |
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| Gene |
CRPPA |
| Chromosomal Location |
7p21.2 |
| Allelic Variant 2 |
; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 7; MDDGA7 |
| Identified Mutation |
c.1183A>T (p.Arg395Ter) |
| Demographic Data |
| Relation to Proband |
proband |
| Age at Sampling |
12 YR |
| Sex |
Female |
| Age of Onset(If not a control) |
6 MO |
| Age at Diagnosis(If not a control) |
11 YR |
| Racial Category |
White |
| Country |
USA |
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| Data Elements |
| Clinical Element Type: General NIGMS Catalog Remarks |
| (Baseline) |
| Mutation Information |
| Gene, variant, consequence, and exon number: |
CRPPA(ISPD), C.1114_1116DEL (P.VAL372DEL), DELETION, EXON 8 |
| Zygosity: |
Compound Heterozygous |
| Other variants: |
CRPPA(ISPD), C.1183A>T (P.ARG395TER), NONSENSE, EXON 9 |
| Age of Symptom Onset and Age at Diagnosis |
| Age of Symptom Onset: |
6 MONTHS |
| Age at Diagnosis: |
11 YEARS |
| In Utero History Information |
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| Birth History Information |
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| Dysmorphic Features |
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| Neurological Symptoms |
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Hypotonia
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| Optical and Audiological Symptoms |
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| Musculoskeletal Symptoms |
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Non-ambulatory
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| Additional Information: |
PROXIMAL PATTERN OF MUSCLE WEAKNESS |
| Developmental Milestones |
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| Holding Head Up Without Assistance: |
Achieved and maintained |
| Sitting Without Assistance: |
Achieved but not maintained |
| Walking Without Assistance: |
Achieved but not maintained |
| Running: |
Not achieved and not maintained |
| Additional Information: |
MAXIMUM MOTOR FUNCTION ABILITY ACHIEVED WAS CLIMBING STAIRS WITH HANDRAIL AT 4-5 YEARS |
| Gastrointestinal Symptoms |
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| Genitourinary Symptoms |
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| Respiratory and Cardiovascular Symptoms |
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| Cognitive and Behavioral Symptoms |
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| Additional Information |
| Testing Performed |
| Neurological Testing: |
BRAIN MRI: NORMAL
SUBGRAVITY NECK AND TRUNK FLEXION (4.5 YEARS AGE) |
| Musculoskeletal and Developmental Testing: |
MUSCLE BIOPSY AT 1 YEAR OF AGE: DYSTROHPIC
MUSCLE BIOPSY: LAMININ ALPHA-2 POSITIVE, ALPHA-DYSTROGLYCAN GLYCOEPITOPE IIH6 MANY FIBERS NEGATIVE, ALPHA-DYSTROGLYCAN CORE 20 POSITIVE |
| Respiratory and Cardiovascular Testing: |
ECG: NORMAL |
| Metabolic, Hematologic, and Endocrinologic Testing: |
SERUM CREATINE KINASE: 5000/1 YEAR, 7000/CURRENT
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| Treatments and Assistive Devices |
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| Medications |
| Family History |
| Remarks |
Clinically affected; case 5 of Cirak et al. 2013 (PMID: 23288328); phenotype classification is congenital muscular dystrophy/limb-girdle muscular dystrophy with no mental retardation; hypotonia was noted during the first year of life, but the subsequent disease course is LGMD-like, making the overall phenotype intermediate CMD/LGMD-like; symptom onset at 6 months of age; non-ambulant; proximal pattern of muscle weakness; normal brain MRI; diagnosis confirmed by: creatine kinase level (5000 IU/L at 1 year; 7000 IU/L at 12 years), muscle biopsy, skin biopsy, brain MRI (normal), electrocardiogram (ECG); reduced movement in legs at 1 year; motor function maintained: holding head up without assistance; motor functions achieved but not maintained: sitting without assistance, walking without assistance; motor function never achieved: running; maximum motor function ability achieved was climbing stairs with handrail at 4-5 years; currently not on breathing support; heart and eye not affected; compound heterozygous mutations in ISPD gene identified by Next Generation exome sequencing; heterozygous premature stop codon mutation in exon 8: c.1114_1116del (p.Val372del); heterozygous in-frame triplet deletion in exon 9 : c.1183A>T (p.Arg395*); muscle biopsy at age 1 year; positive laminin alpha-2 at 80kDa epitope and slight reduction at 300 kDa epitope; many fibres negative for alpha-dystroglycan (glycoepitope IIH6); VIA4-1 traces; positive alpha-dystroglycan (core 20); the wheat germ agglutinin-enriched lysate from the muscle biopsy showed alpha-dystroglycan hypoglycosylation - lack of binding affinity to glycoepitope-specific antibodies IIH6 and VIA4-1; clinically normal mother is GM23332 (fibroblast); clinically normal father is GM23333 (fibroblast). |
| Cirak S, Foley AR, Herrmann R, Willer T, Yau S, Stevens E, Torelli S, Brodd L, Kamynina A, Vondracek P, Roper H, Longman C, Korinthenberg R, Marrosu G, Nürnberg P, UK10K Consortium P, Michele DE, Plagnol V, Hurles M, Moore SA, Sewry CA, Campbell KP, Voit T, Muntoni F, ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies Brain : a journal of neurology136:269-81 2013 |
| PubMed ID: 23288328 |
| Passage Frozen |
10 |
| 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 |
| Substrate |
Gelatin |
| Supplement |
- |
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