Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumor s is seen in the disorder multiple leiomyomatosis (ML). We undertook a geno mewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype con struction and analysis of recombinations permitted the minimal interval con taining the locus, which we have designated "MCUL1," to be refined to an si milar to 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss s tudies of tumors indicated that MCUL1 may act as a tumor suppressor. Identi fication of MCUL1 should have wide interest, since this gene may harbor low -penetrance variants predisposing to the common form of uterine fibroids an d/or may undergo somatic mutation in sporadic leiomyomata.