Homozygosity and linkage disequilibrium mapping of autosomal recessive distal myopathy (Nonaka distal myopathy)

Autosomal recessive distal myopathy or Nonaka distal myopathy (NM) is chara cterized by its unique distribution of muscular weakness and wasting. The p atients present with spared quadriceps muscles even in a late stage of the disease. The hamstring and tibialis anterior muscles are affected severely in early adulthood. We have localized the NM gene to the region between mar kers D9S319 and D9S276 on chromosome 9 by linkage analysis. To further refi ne the localization of the NM gene, we conducted homozygosity and linkage d isequilibrium analysis for 14 patients from I I NM families using IS polymo rphic markers. All of the patients from consanguineous NM families were fou nd to be homozygous for six markers located within the region between marke rs D9S2178 and D9S1859. We also provided evidence for significant allelic a ssociations between the NM region and five marker loci. Examination of the haplotype analysis identified a predominant ancestral haplotype comprising the associated alleles 199-160-154-109 (marker order: D9S2179-D9S2180-D9S21 81-D9S1804) , present in 60% of NM chromosomes and in 0% of parent chromoso mes. On the basis of the data obtained in this study, the majority of NM ch romosomes were derived from a single ancestral founder, and the NM gene is probably located within the 1.5-Mb region between markers D9S2178 and D9S17 91.