%0 Journal Article
%T Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies
%A Matteo Bovolenta
%A Marcella Neri
%A Elena Martoni
%A Anna Urciuolo
%A Patrizia Sabatelli
%A Marina Fabris
%A Paolo Grumati
%A Eugenio Mercuri
%A Enrico Bertini
%A Luciano Merlini
%A Paolo Bonaldo
%A Alessandra Ferlini
%A Francesca Gualandi
%J BMC Medical Genetics
%D 2010
%I BioMed Central
%R 10.1186/1471-2350-11-44
%X We have designed a custom oligonucleotide CGH array in order to investigate the presence of CNVs in the coding and non-coding regions of COL6A1, A2, A3, A5 and A6 genes and a group of genes functionally related to collagen VI. A cohort of 12 patients with UCMD/BM negative at sequencing analysis and 2 subjects carrying a single COL6 mutation whose clinical phenotype was not explicable by inheritance were selected and the occurrence of allelic and genetic heterogeneity explored.A deletion within intron 1A of the COL6A2 gene, occurring in compound heterozygosity with a small deletion in exon 28, previously detected by routine sequencing, was identified in a BM patient. RNA studies showed monoallelic transcription of the COL6A2 gene, thus elucidating the functional effect of the intronic deletion. No pathogenic mutations were identified in the remaining analyzed patients, either within COL6A genes, or in genes functionally related to collagen VI.Our custom CGH array may represent a useful complementary diagnostic tool, especially in recessive forms of the disease, when only one mutant allele is detected by standard sequencing. The intronic deletion we identified represents the first example of a pure intronic mutation in COL6A genes.Mutations in the genes encoding collagen VI (COL6A1, COL6A2 and COL6A3) result in two major phenotypes: Bethlem myopathy [BM, OMIM #158810] and Ullrich congenital muscular dystrophy [UCMD, OMIM #254090]. Despite BM being classically reported as an autosomal dominant condition due to heterozygous COL6 mutations [1,2], we and others have recently described autosomal recessive BM patients [3,4]. In contrast, the allelic form UCMD was initially considered to be an autosomal recessive disorder, with homozygous or compound heterozygous mutations occurring in all three COL6 genes [2], although a few double heterozygous mutations in two different COL6 genes have also been described [5]. Recently, however, up to 50% of UCMD cases have been found to c
%U http://www.biomedcentral.com/1471-2350/11/44