2. Academic Validation
  3. Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome in the context of inherited lipodystrophies

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

  • Metabolism. 2015 Nov;64(11):1530-40. doi: 10.1016/j.metabol.2015.07.022.
Frederic Reinier 1,  Magdalena Zoledziewska 2,  David Hanna 3,  Josh D Smith 3,  Maria Valentini 4,  Ilenia Zara 4,  Riccardo Berutti 4,  Serena Sanna 2,  Manuela Oppo 5,  Roberto Cusano 4,  Rosanna Satta 6,  Maria Antonietta Montesu 6,  Chris Jones 4,  Decio Cerimele 6,  Deborah A Nickerson 3,  Andrea Angius 7,  Francesco Cucca 8,  Francesca Cottoni 6,  Laura Crisponi 9
Affiliations

Affiliations

  • 1 Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • 2 Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
  • 3 Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • 4 Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
  • 5 Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
  • 6 Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche-Dermatologia-Università di Sassari, Italy.
  • 7 Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
  • 8 Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy; Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
  • 9 Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy. Electronic address: laura.crisponi@irgb.cnr.it.
PMID: 26350127 DOI: 10.1016/j.metabol.2015.07.022
Abstract

Background: 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.

Keywords

Exome sequencing; Lipodystrophies; MDPL syndrome; POLD1.

Figures