Abstract
Background. Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome is a recently recognized genetic disorder comprised of mandibular hypoplasia, deafness, progeroid features, and lipodystrophy. It is caused by an autosomal dominant mutation in the POLD1 gene, with <20 genetically confirmed cases to date. Clinical overlap with other progeroid syndromes including Werner syndrome (WS) can present diagnostic challenges. Case. The proband is a 36-year-old male of Sicilian ancestry who was phenotypically normal at birth. Onset of lipodystrophic and progeroid features began at 18 months, with progressive loss of subcutaneous fat, prominent eyes, and pinched nose. Over the next 2 decades, he developed hearing loss, small fingers, joint contractures, hypogonadism, osteoporosis, and hypertriglyceridemia. Three of his 4 siblings had premature hair graying and loss, severe bilateral cataracts, skin changes, and varying degrees of age-related metabolic conditions, raising suspicion for a genetic progeroid syndrome. Genetic Analysis. A targeted sequencing panel identified a heterozygous WRN mutation in the proband's genomic DNA. Sanger sequencing further revealed his parents and an asymptomatic brother to be c...Continue Reading
References
Oct 14, 2004·Clinical Genetics·R L Pollex, R A Hegele
Sep 19, 2009·American Journal of Medical Genetics. Part a·L GaravelliG Novelli
Jul 16, 2010·The Journal of Clinical Endocrinology and Metabolism·Savitha ShastryAbhimanyu Garg
Jan 21, 2012·Human Heredity·Margarida C LopesEleftheria Zeggini
Jun 13, 2012·Nucleic Acids Research·Ngak-Leng SimPauline C Ng
Jun 22, 2012·Human Molecular Genetics·Jemima BarrowmanSusan Michaelis
Jun 19, 2013·Nature Genetics·Michael N WeedonAndrew T Hattersley
Jan 10, 2014·Gerontology·Junko Oshima, Fuki M Hisama
Feb 4, 2014·Nature Genetics·Martin KircherJay Shendure
Feb 8, 2014·Journal of Lipid Research·Christopher T JohansenRobert A Hegele
Dec 6, 2014·The Canadian Journal of Cardiology·Sali M K FarhanRobert A Hegele
Feb 19, 2015·Current Opinion in Lipidology·Robert A HegeleJian Wang
Jul 15, 2015·Human Mutation·Davor LesselChristian Kubisch
Aug 8, 2015·Journal of Medical Genetics·Sali M K FarhanRobert A Hegele
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
May 20, 2017·Metabolism: Clinical and Experimental·Sahar ElouejAnnachiara De Sandre-Giovannoli
Oct 4, 2017·Human Molecular Genetics·Sali M K FarhanJamie M Kramer
Citations
Aug 9, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert A Hegele, Jacqueline S Dron
Feb 12, 2020·BMC Medical Genomics·Jacqueline S DronRobert A Hegele
Dec 29, 2020·American Journal of Medical Genetics. Part a·Pui Tak YuFm Ivan Lo
Jun 10, 2021·The Application of Clinical Genetics·Fabio Coppedè