To the Editor: Dunnigan-Köbberling syndrome or familial partial lipodystrophy (FPL) is an inherited form of partial lipodystrophy characterised by selective loss of subcutaneous limb and gluteal fat, and excess facial fat deposition [1]. Some authors have suggested that FPL be subclassified into Dunnigan and Köbberling subtypes [2], the key difference being the loss of subcutaneous truncal fat in the Dunnigan subtype; this depot is preserved or increased in Köbberling FPL. Although the molecular mechanisms responsible for the unusual fat distribution seen in FPL remain unknown, the majority of cases are the result of heterozygous mutations in the LMNA gene (dominantnegative mutations in PPARG account for some of the remainder). Lamin A/C is principally a structural nuclear envelope protein which, like other intermediate filament proteins, consists of a central α-helical coiled-coil rod domain flanked by two globular domains. To date, the majority of mutations associated with FPL have been confined to exons 8 and 11 of LMNA, both of which contribute to the carboxy-terminal immunoglobulin-like globular domain. Structural modelling of this region suggests that the exon 8 FPL mutations occupy a discrete superficial patch on this globular domain [3] and are likely to alter protein–protein interactions either between lamin proteins themselves or between lamin proteins and other nuclear elements. As LMNA mutations are currently the most common explanation for inherited forms of partial lipodystrophy, we routinely sequence exons 8 to 12 in all probands with partial lipodystrophy.

Three unrelated Caucasian pedigrees harbouring a novel heterozygous LMNA serine-583-leucine (S583L; nt-1748 [C→ T]) mutation in exon 11 were identified (Table 1). The S583L variant was associated with a stereotyped pattern of partial lipodystrophy in which subcutaneous limb and gluteal fat was lost but subcutaneous abdominal, facial and neck fat was preserved (Fig. 1). This Köbberling-type FPL phenotype was apparent in kindreds A, B and C, and is consistent with that previously described in carriers of a mutation in the preceding residue (R582H)[4]. It was suggested that the fact that the R582H mutation is lamin A specific (exon 11 is not tran-