• familial partial lipodystrophy type 2

This report describes lipodystrophy, familial partial, type 2 (FPLD2); FPLD2 exhibits autosomal dominant inheritance. The human gene implicated in this disease is lamin A/C (LMNA), which encodes an intermediate filament protein that is a component of the nuclear lamina. There are multiple lamins in both humans and flies: the human genes LMNA, LMNB2 and LMNB1 are orthologous to fly genes Dmel\Lam and Dmel\LamC. Classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes.

The human LMNA gene is implicated in many diseases (see MIM:150330) including multiple forms of muscular dystrophy: Emery-Dreifuss muscular dystrophy 2 and 3 (MIM:181350, MIM:616516, FBhh0000209), and LMNA-related congenital muscular dystrophy (MIM:613205, FBhh0000293). Additional diseases include lipodystrophy (subject of this report), Hutchinson-Gilford progeria syndrome (MIM:176670, FBhh0000176) and dilated cardiomyopathy 1A (MIM:115200, FBhh0000157). See also the human disease report 'laminopathies' (FBhh0000264).

Multiple UAS and heat-shock constructs of the human Hsap\LMNA gene have been introduced into flies, including wild-type LMNA, mutant protein isoforms, and deletion constructs.

In the case of FPLD2, analogous mutations in LamC fly gene have been used to characterize variants implicated in human disease; see the 'Disease-Implicated Variants' table below. Effects of specific variants can be quite variable; the use of Drosophila allows for comparisons of the effects of specific mutations in a nearly identical genetic background. It has been shown that two different mutant lamins possess different patterns of subcellular localization in muscle and have opposing effects on nuclear morphology and muscle function.

[updated Jul. 2023 by FlyBase; FBrf0222196]