Hereditary benign chorea - Clinical and genetic features of a distinct disease

Objective To describe a second family with benign hereditary chorea (BCH, O MIM 118700) and suggestive Linkage to chromosome 14q. BGH is an autosomal d ominant disorder of early onset that differs from Huntington disease in bei ng nondementing and nonprogressive without other neurologic signs. There ha s been controversy regarding the existence of BCH as a discrete disorder. B ackground: A single kindred was recently reported with Linkage of BCH to a 20.6-KcM region on chromosome 14q. Methods In a four-generation family with BCH, linkage was evaluated to markers in a 23-KcM region between D14S49 an d D14S66 that contains the putative BCH locus. Results: A multipoint nonpar ametric Iod score of 3.01 is consistent with linkage of disease in this fam ily to the 14q BCH locus. A recombination event in one affected individual enabled the critical region to be narrowed to 6.93 KcM flanked by D14S1068 and D14S1064. This region contains two candidate genes: glial maturation fa ctor beta and guanosine triphosphate cyclohydrolase I (GCH1). Survival moto r neuron (SMN) interacting protein-1 is eliminated as a candidate gene beca use it Lies outside the critical region. No sequence alteration was identif ied in the coding region of GCH1 in an affected individual. Conclusion: The se data provide further evidence that BCH is a distinct entity, narrow the location of BCH to a 6.93-KcM region on chromosome 14q, and exclude SMN int eracting protein-1 as a candidate gene.