Ontology highlight
ABSTRACT: Background
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease.Purpose
To report genetic analysis results in two families in which all known MKS diseases genes have been excluded.Methods
In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration.Results
We identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state.Conclusions
TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies.
SUBMITTER: Shaheen R
PROVIDER: S-EPMC3585488 | biostudies-literature | 2013 Mar
REPOSITORIES: biostudies-literature
Shaheen Ranad R Ansari Shinu S Mardawi Elham Al EA Alshammari Muneera J MJ Alkuraya Fowzan S FS
Journal of medical genetics 20130124 3
<h4>Background</h4>Meckel-Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease.<h4>Purpose</h4>To report genetic analysis results in two families in which all known MKS diseases genes have been excluded.<h4>Methods</h4>In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequenc ...[more]