A POINT MUTATION IN THE GLYCEROL KINASE GENE ASSOCIATED WITH A DELETION IN THE DYSTROPHIN GENE IN A FAMILIAL X-LINKED MUSCULAR-DYSTROPHY - NONCONTIGUOUS GENE SYNDROME INVOLVING BECKER MUSCULAR-DYSTROPHY AND GLYCEROL KINASE LOCI

We report a family with an X-linked recessive muscular dystrophy chara cterised by exercise-induced myalgia, recurrent pigmenturia and mild p roximal muscle involvement. Immunocytochemical and immunoblotting anal ysis in muscle, using the antibody directed against the rod domain of dystrophin, revealed a loss of immunoreactivity, but the immunolabelli ng using the antibodies directed against the COOH and NH2 domains of d ystrophin were almost normal. The immunoreactions for alpha-sarcoglyca n, gamma-sarcoglycan, and beta-dystroglycan were normal. In the five m ale patients of this family with increased serum creatine kinase level s (from x8 to x50), mass spectrometry screening of the urine revealed a large increase in glycerol elimination which was quantified by enzym atic assay (from x14 to x39), An in-frame deletion of the dystrophin g ene (exons 13-29) was found in the same five males and in three carrie r females, All the deleted chromosomes also carried a missense mutatio n at nucleotide 947 of the Xp glycerol kinase (GK) gene resulting in a Thr to Met substitution at codon 278. These findings indicate that th e two mutations cosegregate on the same chromosome in this family. Thi s is the first reported case of two physically independent mutations, within the DMD and GK genes, which are contiguous but several hundred kilobases apart. (C) 1997 Elsevier Science B.V.