Description:
MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2A; LGMD2A
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Muscular Dystrophies |
| Class |
Congenital Muscle Diseases |
| Class |
Disorders with Trinucleotide Expansions |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| creatine kinase |
According to the submitter, biochemical test results for this subject showed increased enzyme activity. EC Number: 2.7.3.2 |
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| Gene |
CAPN3 |
| Chromosomal Location |
15q15.1-q21.1 |
| Allelic Variant 1 |
114240.0010; LIMB-GIRDLE MUSCULAR DYSTROPHY, TYPE 2A |
| Identified Mutation |
ARG490GLN |
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| Gene |
CAPN3 |
| Chromosomal Location |
15q15.1-q21.1 |
| Allelic Variant 2 |
THR184ARGfs*36; LIMB-GIRDLE MUSCULAR DYSTROPHY, TYPE 2A |
| Identified Mutation |
THR184ARGfs*36 |
| Remarks |
Clinically affected; progressive bilateral weakness of arms and legs; wheelchair-dependent; weak facial muscles; scapular winging; elevated serum CPK; no chromosome 4 contraction; normal methylation levels; D4Z4 repeats for this donor subject are as follows: at 4q35: 28/59 copies (clinically unaffected individuals usually have >10 D4Z4 repeats on both alleles at chromosome 4q35) and at 10q26: 5/22 copies; this patient presented with FSHD symptoms, but does not have typical D4Z4 repeats (an occurrence in about 5% of cases); for additional genetic and epigenetic characterization, D4Z4 allele sizes, subtelomeric polymorphisms and methylation were tested using pulsed-field gel electrophoresis and Southern blotting with non-radioactive digoxigenin-labeled probes (Leidenroth et al. Eur J Hum Genet, 2012,PMID 22378277); GM17726 has three A-type telomeres and four D4Z4 alleles - the two larger alleles are from chromosome 4 while two smaller alleles are from chromosome 10; the original diagnosis was indicated as non-4q FSHD; Leidenroth et al. (2012) used whole exome sequencing to identify two known pathogenic mutations in CAPN3: a heterozygous G>A transition resulting in a substitution (Arg490Gln) and a 1 bp deletion of adenine in exon 4 causing a frameshift (Thr184Argfs*36); RT-PCR and Sanger sequencing confirmed that the two mutations are on different chromosomes; this compound heterozygous mutation in CAPN3 indicates a diagnosis of LGMD2A and not FSHD. |
| Leidenroth A, Sorte HS, Gilfillan G, Ehrlich M, Lyle R, Hewitt JE, Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole-exome analysis European journal of human genetics : EJHG20:999-1003 2012 |
| PubMed ID: 22378277 |
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