Confirmation of linkage of hereditary partial lipodystrophy to chromosome 1q21-22

Familial lipodystrophy is a genetically heterogeneous set of disorders char acterized by a total or partial absence of subcutaneous fat, diabetes melli tus or impaired glucose tolerance, hyperlipidemia, and hypermetabolism [Sen ior and Gellis, 1964], One subtype, familial partial lipodystrophy Dunnigan (FPLD), is a rare autosomal dominant trait that results in an gradual loss of subcutaneous fat in the lower trunk: and limbs, Type V hyperlipoprotein emia, hypertriglyceridemia, and insulin-resistant diabetes, Previous report s of this condition have been limited to case reports or very small familie s, Recently, Peters et al, reported on linkage of five families of Western European descent to a 5.3 cM region on chromosome 1q21-22 between the flank ing markers D1S305 and D1S1600 [Peters et al,, 1998: Nat Genet 18:292-295], We performed linkage and haplotype analysis using highly polymorphic, micr osatellite markers on a large, multigeneration Caucasian kindred of German ancestry. The maximum two-point lod score achieved was 4.96 at theta(max) = 0 for marker D1S2721, Multipoint analysis gave an overall maximum lod scor e of 6.27 near marker D1S2721, The results of the haplotype analysis suppor t the minimal candidate region as reported by Peters et al, (C) 1999 Wiley- Liss, Inc.