Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome in the context of inherited lipodystrophies

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• 作者：Frederic Reinier^a ; ^b ; Magdalena Zoledziewska^c ; David Hanna^b ; Josh D. Smith^b ; Maria Valentini^a ; Ilenia Zara^a ; Riccardo Berutti^a ; Serena Sanna^c ; Manuela Oppo^a ; ^d ; Roberto Cusano^a ; Rosanna Satta^e ; Maria Antonietta Montesu^e ; Chris Jones^a ; Decio Cerimele^e ; Deborah A. Nickerson^b ; Andrea Angius^a ; ^c ; Francesco Cucca^c ; ^d ; ¹ ; Francesca Cottoni^e ; ¹ ; Laura Crisponi^c ; ¹ ; ^{laura.crisponi@irgb.cnr.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CGL ; Congenital generalized lipodystrophy ; FPLD ; familial partial lipodystrophy ; T2D ; type 2 diabetes ; MADA ; Mandibuloacral dysplasia type A ; MADB ; Mandibuloacral dysplasia type A ; MDPL ; Mandibular hypoplasia ; deafness ; progeroid features and lipodystrophy syndrome ; HGPS ; Hutchinson&ndash ; Gilford progeria syndrome ; WRN ; Werner syndrome ; PRAAS ; Proteasome-associated autoinflammatory syndromes&ndash ; Autoinflammatory Lipodystrophy syndrome ; SHORT ; Short stature ; hyperextensibility of joints and/or
• 刊名：Metabolism
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：64
• 期：11
• 页码：1530-1540
• 全文大小：711 K

文摘

Lipodystrophies are a large heterogeneous group of genetic or acquired disorders characterized by generalized or partial fat loss, usually associated with metabolic complications such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis. Many efforts have been made in the last years in identifying the genetic etiologies of several lipodystrophy forms, although some remain to be elucidated.

Methods

We report here the clinical description of a woman with a rare severe lipodystrophic and progeroid syndrome associated with hypertriglyceridemia and diabetes whose genetic bases have been clarified through whole-exome sequencing (WES) analysis.

Results

This article reports the 5th MDPL (Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome) patient with the same de novo p.S605del mutation in POLD1. We provided further genetic evidence that this is a disease-causing mutation along with a plausible molecular mechanism responsible for this recurring event. Moreover we overviewed the current classification of the inherited forms of lipodystrophy, along with their underlying molecular basis.

Conclusions

Progress in the identification of lipodystrophy genes will help in better understanding the role of the pathways involved in the complex physiology of fat. This will lead to new targets towards develop innovative therapeutic strategies for treating the disorder and its metabolic complications, as well as more common forms of adipose tissue redistribution as observed in the metabolic syndrome and type 2 diabetes.