Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome in the context of inherited lipodystrophies.
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.
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Frederic
F
Reinier
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
Magdalena
M
Zoledziewska
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
David
D
Hanna
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Josh D
JD
Smith
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
Maria
M
Valentini
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
Ilenia
I
Zara
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
Riccardo
R
Berutti
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
Serena
S
Sanna
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy; Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
Manuela
M
Oppo
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
Roberto
R
Cusano
Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche-Dermatologia-Università di Sassari, Italy.
Rosanna
R
Satta
Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche-Dermatologia-Università di Sassari, Italy.
Maria Antonietta
MA
Montesu
Centre for Advanced Studies, Research and Development in Sardinia (CRS4), Pula, Italy.
Chris
C
Jones
Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche-Dermatologia-Università di Sassari, Italy.
Decio
D
Cerimele
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Deborah A
DA
Nickerson
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.
Andrea
A
Angius
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy; Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy.
Francesco
F
Cucca
Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche-Dermatologia-Università di Sassari, Italy.
Francesca
F
Cottoni
Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy. Electronic address: laura.crisponi@irgb.cnr.it.
Laura
L
Crisponi
D000328:Adult; D003638:Deafness / Q000235:genetics*; D005260:Female; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008336:Mandibular Diseases / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
Exome sequencing; Lipodystrophies; MDPL syndrome; POLD1