- Author:
Wanglong CAO
1
;
Yanan ZHANG
;
Changgao ZHONG
;
Guangxiu LU
;
Yueqiu TAN
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Collagen Type VI; genetics; Contracture; genetics; Exons; Female; Heterozygote; Humans; Male; Middle Aged; Molecular Sequence Data; Muscular Dystrophies; congenital; genetics; Mutation, Missense; Pedigree; Young Adult
- From: Chinese Journal of Medical Genetics 2014;31(6):698-702
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo determine the molecular etiology for a muscular dystrophy pedigree with target region sequencing platform using hereditary myopathy capture array.
METHODSSpecific gene testing was performed based on the clinical diagnosis. Since no pathogenic mutation was found, target region sequencing with hereditary myopathy capture array combined with Sanger sequencing and bioinformatics analysis were employed in turn. PolyPhen and NCBI were used to evaluate the pathogenicity of identified mutation and conservation of the gene.
RESULTSTarget region sequencing indicated the proband has carried a heterozygous c.3353 A>C mutation of COL6A3 gene, which was confirmed by Sanger-sequencing in 4 affected individuals from the family. The same mutation was not detected in healthy members of the pedigree. Bioinformatics analysis suggested that the mutation has caused a highly pathogenic amino acid substitution from Histidine to Proline. The affected patients featured normal intelligence with mild myogenic damage by muscle biopsy, slightly increased serum creatine kinase and slow disease progression, which was consistent with Bethlem myopathy.
CONCLUSIONTarget region sequencing is an effective and efficient method for genetic testing. The heterozygous c.3353A>C mutation in exon 8 of the COL6A3 gene probably underlies the Bethlem myopathy with autosomal dominant inheritance.