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Short report
Mutations in TMEM231 cause Meckel–Gruber syndrome
  1. Ranad Shaheen1,
  2. Shinu Ansari1,
  3. Elham AL Mardawi2,
  4. Muneera J Alshammari1,3,
  5. Fowzan S Alkuraya1,4
  1. 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  2. 2Department of Obstetrics and Gynecology, Security Forces Hospital, Riyadh, Saudi Arabia
  3. 3Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
  4. 4Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Fowzan S Alkuraya, Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh 11211, Saudi Arabia; falkuraya{at}


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.

  • TMEM231
  • Joubert
  • Ciliopathy
  • Autozygome
  • Exome

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