Structural organization, complete genomic sequences and mutational analyses of the Fukuyama-type congenital muscular dystrophy gene, fukutin

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessiv e severe muscular dystrophy in combination,vith cerebral cortical dysplasia , Previously, we identified the gene responsible for FCMD, termed fukutin, through positional cloning. In this study, we have sequenced 131 892 bp of genomic DNA in the region of the fukutin gene on chromosome 9q31 and obtain ed its complete genomic structure. The fukutin genomic sequence spans appro ximately 100 kb and is organized into 10 exons (41-6067 bp) and nine intron s (1841-21 460 bp), Using these sequence data, me have identified three nov el fukutin mutations in FCMD patients. We have also located a putative TATA box in the flanking 5 ' region and identified numerous alternatively splic ed fukutin mRNA transcripts. Analysis of expressed sequence tag clusters wi thin the region revealed two novel genes upstream of the fukutin gene, Thes e data provide fundamental information to support detailed genetic and func tional analyses of the fukutin gene. (C) 2001 Federation of European Bioche mical Societies. Published by Elsevier Science B.V. All rights reserved.