Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a 1.4-cM region of 1q23

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessi ve syndrome characterized by megaloblastic anemia, deafness, and diabetes m ellitus. A genome scan previously established linkage of this disorder to 1 q23 and haplotype analysis defined a 16-cM critical region. Molecular genet ic analyses of four unrelated multiplex iranian families inheriting TRMA co nfirmed linkage to the same region and identified recombinant chromosomes w hich permitted refinement of the critical region to a narrow 1.4-cM interva l. The haplotypes of the families differed, consistent with at least two in dependent mutational events, This refinement of the TRMA locus to less than 10% of that previously published should markedly facilitate the identifica tion and evaluation of positional candidate and novel genes which may cause this disorder. (C) 1999 Academic Press.