Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL)

Metabolism: Clinical and Experimental
Sahar ElouejAnnachiara De Sandre-Giovannoli

Abstract

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Twelve unrelated patients carried a recurrent in-frame deletion of a single codon (p.Ser605del) and two other patients carried a novel heterozygous mutation in exon 13 (p.Arg507Cys). Additionally and interestingly, germline mutations of the same gene have been involved in familial polyposis and colorectal cancer (CRC) predisposition. We describe a male and a female patient with MDPL respectively affected with mild and severe phenotypes. Both of them showed mandibular hypoplasia, a beaked nose with bird-like facies, prominent eyes, a small mouth, growth retardation, muscle and skin atrophy, but the female patient showed such a severe and early phenotype that a first working diagnosis of Hutchinson-Gilford Progeria was made. The exploration was performed by direct sequenc...Continue Reading

Citations

Nov 6, 2018·DNA and Cell Biology·Chiara FiorilloGiuseppe Novelli
Jul 7, 2019·Life Science Alliance·Stanislaw K JozwiakowskiKerstin Gari
May 6, 2020·Expert Review of Endocrinology & Metabolism·Maria C Foss-FreitasElif A Oral
Aug 30, 2020·Clinical Genetics·Franziska SchnabelBernd Wollnik
Oct 5, 2019·Nature Structural & Molecular Biology·Rinku JainAneel K Aggarwal
Aug 27, 2019·The Journal of Clinical Investigation·Cecilia Domínguez CondeKaan Boztug
Sep 13, 2020·Nature Communications·Sahar ElouejAnnachiara De Sandre-Giovannoli
Jun 4, 2018·Nucleic Acids Research·Jean-Pierre DesvignesDavid Salgado
Jan 23, 2021·International Journal of Molecular Sciences·Megan Schmit, Anja-Katrin Bielinsky
Nov 4, 2020·Journal of Clinical Immunology·Diana X Nichols-VinuezaLuigi D Notarangelo
Nov 19, 2020·Proceedings of the National Academy of Sciences of the United States of America·Fengwei ZhengMichael E O'Donnell
Apr 18, 2021·European Journal of Ophthalmology·Lin ZhouZhuping Xu
Jun 10, 2021·The Application of Clinical Genetics·Fabio Coppedè

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