Somatic Cell and Molecular Genetics, Vol. 17, No. 4, I 991, pp. 421-425 Brief Communication Huntington Disease-Linked Locus D4Slll Exposed as the C~-L-Iduronidase Gene Marcy E. MacDonald, ~ Hamish S. Scott, z William L. Whaley, ~ Thomas Pohl, 3 John J. Wasmuth, ~ Hans Lehrach, 5 C. Phillip Morris, 2 Anne-Marie Frischauf, 5 John J. Hopwood, ~ and James F. Gusella ~ Weurogenetics Laboratory, Massachusetts"General Hospital and Department of Genetics, Harvard Medical School, Bos- ton, Massachusetts' 02114; 2Lysosomal Diseases Research Unit, Depanment of Chemical Pathology, Adelaide Children's Hospital, North Adelaide, S.A. 5006, Australia; 3EMBL, P.O. Box 1022.40, D6900, HeiIdelberg, Germany; 4Department of Biological Chemistry, University of California, Irvine, California 92717; and Slmperial Cancer Research Fund, Lin- coln's Inn Fields, London, WC2A 3PX, U.K. Received 8 March 1991 Abstraet--~x-L-Iduronidase (IDUA) has been intensively studied due to its causative rote in mucopolysaccharidosis type I (Hurler, Scheie and Hurler/Scheie syndromes). The recent cloning of a human IDUA cDNA has resulted in a reevaluation of the chromosomal location of this gene. Previously assigned to chromosome 22, IDUA now has been localized to 4p16.3, the region of chromosome 4 associated with Huntington's disease (HD). The existence of a battery of cloned DNA, physical map information, and genetic polymorphism data for this region has allowed the rapid fine mapping of lDUA within the terminal cytogenetic band of 4p. IDUA was found to be coincident with D4Sl11, an anonymous locus displaying a highly informative multiallele DNA polymorphism. This map location, 1.1 x 106 bp from the wlomere, makes IDUd the most distal cIoned gene assigned to 4p. However, it falls within a segment of 4p16.3 that has been eliminated fi'om the HD candidate region, excluding a role for IDUA in this disorder. INTRODUCTION Huntington's disease (HD) is a late- onset disorder caused by an autosomal dominant defect mapping in 4p16.3 (1). The disease is characterized by progressive cho- rea, psychiatric disturbance, and intellectual decline due to loss of striatal neurons. Symptoms typically appear in middle age, and death ensues in 10-20 years, after an inexorable decline that currently cannot be prevented or delayed by therapy. Many cloned genes, including candidates such as the two GABA receptor subunits (GABRA2, GABRB1) (2), and dihydropteridine reduc- tase (QDPR) (3) have been mapped on chromosome 4p, but none has been assigned within the immediate vicinity of HD, which lies in the terminal cytogenetic subband, a region expected to contain 6 x 106 bp (4). An intensive effort has been undertaken to isolate the HD gene based on its chromo- somal position and has produced detailed genetic and physical maps of the 4p telomeric region (5-9). In addition, much of the candidate region has been isolated as cloned DNA (9-11). To date, it has not been pos- sible to place the liD gene in an unequivocal position on the physical map, due to the existence of contradictory recombination events in HD kindreds (5). Two candidate regions must be considered, one spanning 421 0740-7750/91/0700-0421506.50/0 © 1991 Plenum Publishing Corporation