@article{cfd2d657f2f8449994e5d0843cee374f,
title = "TMEM231 Gene Conversion Associated with Joubert and Meckel–Gruber Syndromes in the Same Family",
abstract = "Joubert and Meckel–Gruber syndromes (JS and MGS) are ciliopathies with overlapping features. JS patients manifest the “molar tooth sign” on brain imaging and variable eye, kidney, and liver disease. MGS presents with polycystic kidneys, occipital encephalocele, and polydactyly; it is typically perinatally fatal. Both syndromes are genetically heterogeneous; some genes cause either syndrome. Here, we report two brothers married to unrelated women. The first brother had three daughters with JS and a son with polycystic kidneys who died at birth. The second brother's wife had a fetal demise due to MGS. Whole exome sequencing identified TMEM231 NM_001077416.2: c.784G>A; p.(Asp262Asn) in all children and the wife of the first brother; the second brother's wife had a c.406T>G;p.(Trp136Gly) change. In-depth analysis uncovered a rare gene conversion event in TMEM231, leading to loss of exon 4, in all the affected children of first brother. We believe that the combination of this gene conversion with different missense mutations led to a spectrum of phenotypes that span JS and MGS.",
keywords = "TMEM231, cilia, gene conversion, translocation, whole exome sequencing",
author = "{NISC Comparative Sequencing Program} and Dino Maglic and Joshi Stephen and Malicdan, {May Christine V.} and Jennifer Guo and Roxanne Fischer and Daniel Konzman and Mullikin, {James C.} and Gahl, {William A.} and Thierry Vilboux and Meral Gunay-Aygun",
note = "Funding Information: The authors thank the Joubert Syndrome and Related Disorders Foundation for their extensive support and the patients and their families who generously participated in this investigation. This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, Maryland, USA. D.M. is funded by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. For a complete list, please visit the Foundation website at: http://fnih.org/work/education-training-0/medical-research-scholars-program. The authors do not have a conflict of interest to declare. Publisher Copyright: {\textcopyright} 2016 WILEY PERIODICALS, INC.",
year = "2016",
month = nov,
day = "1",
doi = "10.1002/humu.23054",
language = "English (US)",
volume = "37",
pages = "1144--1148",
journal = "Human mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "11",
}