Mutations in TMEM231 cause Meckel-Gruber syndrome.
BACKGROUND
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease.


OBJECTIVE
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.
Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia. falkuraya@kfshrc.edu.sa
Ranad
R
Shaheen
Shinu
S
Ansari
Elham Al
EA
Mardawi
Muneera J
MJ
Alshammari
Fowzan S
FS
Alkuraya
D000022:Abortion, Spontaneous; D000595:Amino Acid Sequence; D002925:Ciliary Motility Disorders / Q000235:genetics*; D003241:Consanguinity; D004677:Encephalocele / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D007690:Polycystic Kidney Diseases / Q000235:genetics*; D011247:Pregnancy; D012174:Retinitis Pigmentosa; D016415:Sequence Alignment
D008565:Membrane Proteins; C578841:TMEM231 protein, human