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TMEM231Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family

Authors :
Meral Gunay-Aygun
Joshi Stephen
Daniel Konzman
Jennifer Guo
James C. Mullikin
Roxanne Fischer
Dino Maglic
William A. Gahl
May Christine V. Malicdan
Thierry Vilboux
Source :
Human Mutation. 37:1144-1148
Publication Year :
2016
Publisher :
Hindawi Limited, 2016.

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. This article is protected by copyright. All rights reserved

Details

ISSN :
10597794
Volume :
37
Database :
OpenAIRE
Journal :
Human Mutation
Accession number :
edsair.doi...........04a262ab6d66d3784a0a66c045a1ee67
Full Text :
https://doi.org/10.1002/humu.23054