Mutations in LOXHD1, a recessive-deafness locus, cause dominant late-onset Fuchs corneal dystrophy.

American Journal of Human Genetics
S Amer RiazuddinJohn D Gottsch

Abstract

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico a...Continue Reading

Citations

Oct 22, 2013·Seminars in Ophthalmology·Cecily E HamillUla Jurkunas
Apr 21, 2018·Cornea·Allen O EghrariJohn D Gottsch
Oct 5, 2018·Journal of Speech, Language, and Hearing Research : JSLHR·Nicholas S ReedJohn D Gottsch
Jan 5, 2019·Molecular Diagnosis & Therapy·Jie ZhangDipika V Patel
Jul 6, 2019·Scientific Reports·Darpan MalhotraJoseph R Casey
Nov 11, 2019·Scientific Reports·Peipei PanMatilda F Chan
Nov 12, 2019·The Journal of International Medical Research·Chuan ZhangQinghua Zhang
Mar 21, 2020·Asia-Pacific Journal of Ophthalmology·Li Jia Chen
Apr 11, 2020·Oxidative Medicine and Cellular Longevity·Ming-Xuan WangYa-Juan Zheng
Nov 8, 2013·Journal of Human Genetics·Bahareh RabbaniNejat Mahdieh
Apr 16, 2013·Expert Review of Ophthalmology·Benjamin W IliffJohn D Gottsch
Aug 26, 2014·International Journal of Molecular Sciences·Katarzyna A WojcikJacek P Szaflik
May 1, 2013·Asia-Pacific Journal of Ophthalmology·Benjamin T Whigham, R Rand Allingham
Sep 30, 2018·Investigative Ophthalmology & Visual Science·Liubov O SkorodumovaBoris E Malyugin
Sep 26, 2013·International Journal of Molecular Sciences·Katarzyna A WojcikJacek P Szaflik
Aug 5, 2016·Asia-Pacific Journal of Ophthalmology·Sundar SrilekhaS Sripriya
Sep 22, 2015·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Katarzyna A WójcikJacek P Szaflik
Mar 31, 2017·Nature Communications·Natalie A AfshariSudha K Iyengar
Jul 14, 2018·Eye & Contact Lens·Caterina SarnicolaKathryn Colby
Aug 21, 2018·The Open Ophthalmology Journal·Naoki OkumuraNoriko Koizumi
Sep 17, 2019·Annual Review of Vision Science·Mario MatthaeiAlbert S Jun
Mar 21, 2015·The Annals of Otology, Rhinology, and Laryngology·Kentaro MoriShin-Ichi Usami

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