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TMEM231Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family
- 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
- Subjects :
- 0301 basic medicine
Genetics
congenital, hereditary, and neonatal diseases and abnormalities
Occipital encephalocele
Polydactyly
Genetic heterogeneity
030105 genetics & heredity
Biology
medicine.disease
Brother
Ciliopathies
03 medical and health sciences
Exon
030104 developmental biology
medicine
Missense mutation
Genetics (clinical)
Exome sequencing
Subjects
Details
- ISSN :
- 10597794
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Human Mutation
- Accession number :
- edsair.doi...........04a262ab6d66d3784a0a66c045a1ee67
- Full Text :
- https://doi.org/10.1002/humu.23054