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TMEM231 Gene Conversion Associated with Joubert and Meckel–Gruber Syndromes in the Same Family
Author(s) -
Maglic Dino,
Stephen Joshi,
Malicdan May Christine V.,
Guo Jennifer,
Fischer Roxanne,
Konzman Daniel,
Mullikin James C.,
Gahl William A.,
Vilboux Thierry,
GunayAygun Meral
Publication year - 2016
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23054
Subject(s) - biology , joubert syndrome , genetics , gene
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.