Comparison of Phenotypes in Male and Female Individuals of a New Family with Dunnigan Type of Familial Partial Lipodystrophy Due to a Lamin A/C R482W Mutation

Introduction

The Dunnigan type of familial partial lipodystrophy (FPLD) is characterized by loss of subcutaneous adipose tissue from extremities accompanied by excess fat deposition within the face, the neck, the axilla, and intra-abdominally [1]. A genetic study performed in 2000 identified a missense mutation (R482Q) in exon 8 of the lamin A/C gene on locus 1q21-22 linked to FPLD [1]. Since then, several other mutations have been described in the same exon and fewer mutations in exon 11 [1]. Lamin A/C is a nuclear membrane protein known to interact with transcription factors [2]. Of these, SREBP-1c is important for adipogenesis [2].

Features of the Dunnigan syndrome usually develop after puberty with metabolic alterations including hypertriglyceridemia, and insulin resistance precede abnormalities in fat distribution [3]. It is known that the physical appearance of the syndrome is more pronounced in females, while men are thought to exhibit fat accumulation predominantly in the neck beginning at the age around forty [4]. Also, metabolic abnormalities develop mostly in women. Indeed, in families carrying a special mutation, R482W, male individuals were reported not to develop any metabolic phenotype at all [4]. This has great impact on clinical practice since it suggests that male carriers of this mutation do not need specialized endocrine care, for example, implementation of a leptin therapy.

The aim of the present study was to characterize a newly identified Caucasian family carrying a lamin A/C R482W mutation with respect to metabolic phenotypes and defects in body fat distribution in affected male and female individuals.

References

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