© Georg Thieme Verlag KG Stuttgart · New York
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
09 February 2009 (eFirst)
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 . 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 . Since then, several other mutations have been described in the same exon and fewer mutations in exon 11 . Lamin A/C is a nuclear membrane protein known to interact with transcription factors . Of these, SREBP-1c is important for adipogenesis .
Features of the Dunnigan syndrome usually develop after puberty with metabolic alterations including hypertriglyceridemia, and insulin resistance precede abnormalities in fat distribution . 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 . 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 . 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.
- 1 Schmidt HHJ, Genschel J, Baier P, Schmidt M, Ockenga J, Tietge UJF, Pröpsting M, Büttner C, Manns MP, Lochs H, Brabant G. J Clin Endocrinol Metab. 2001; 86 2289-2295
- 2 Lloyd DJ, Trembath RC, Shackleton S. Hum Mol Genet. 2002; 11 769-777
- 3 Vigouroux C, Magré J, Vantyghem MC, Bourut C, Lascols O, Shackleton S, Lloyd DJ, Guerci B, Padova G, Valensi P, Grimaldi A, Piquemal R, Touraine P, Trembath RC, Capeau J. Diabetes. 2000; 49 1958-1962
- 4 Araújo-Vilar D, Loidi L, Domínguez F, Cabezas-Cerrato J. Horm Metab Res. 2003; 35 29-35
- 5 Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen GL, Williams TD, Lewis H, Schafer AJ, Chatterjee VK, O’Rahilly S. Nature. 1999; 402 880-883
- 6 George S, Rochford JJ, Wolfrum C, Gray SL, Schinner S, Wilson JC, Soos MA, Murgatroyd PR, Williams RM, Acerini CL, Dunger DB, Barford D, Umpleby AM, Wareham NJ, Davies HA, Schafer AJ, Stoffel M, O’Rahilly S, Barroso I. Science. 2004; 304 1325-1328
- 7 Vantyghem MC, Faivre-Defrance F, Marcelli-Tourvieille S, Fermon C, Evrard A, Bourdelle-Hego MF, Vigouroux C, Defebvre L, Delemer B, Wemeau JL. Clin Endocrinol. 2007; 67 247-249
- 8 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Horm Metab Res. 2007; 39 314-321
- 9 Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, Cline GW, DePaoli AM, Taylor SI, Gorden P, Shulman GI. J Clin Invest. 2002; 109 1345-1350
- 10 Dimitriadis G, Boutati E, Raptis SA. Horm Metab Res. 2007; 39 705-706
Dr. M. Laudes
Klinik II und Poliklinik für Innere Medizin
Zentrum für Molekulare Medizin
Universität zu Köln
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