LOCALIZATION OF THE GENE FOR FAMILIAL PARTIAL LIPODYSTROPHY (DUNNIGANVARIETY) TO CHROMOSOME 1Q21-22

Obesity is strongly implicated in the pathophysiology of insulin resis tance, diabetes mellitus and dyslipidemia(1-3). The mechanisms, howeve r, by which obesity causes these complications are not known, The stud y of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipod ystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-domina nt condition characterized by marked loss of subcutaneous adipose tiss ue affecting the trunk and extremities but with excess fat deposition in the head and neck areas(4-14). Affected individuals show an increas ed preponderance of insulin resistance, diabetes mellitus, dyslipidemi a and acanthosis nigricans(4-14). The genetic basis of FPLD is unknown . We carried out a genome-wide scan with a set of highly polymorphic s hort tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21-22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at theta(max) = 0 was 5.84. Multipoint-linkage analysis yi elded a peak lod score of 8.25 between D1S305 and D1S1600. There was n o evidence for genetic heterogeneity (alpha=1) in the pedigrees.