MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

International JSRD Study Group

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14. COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs.

Original languageEnglish (US)
Pages (from-to)E432-E442
JournalHuman mutation
Volume30
Issue number2
DOIs
StatePublished - Feb 2009

Bibliographical note

Funding Information:
Contract grant sponsor: Italian Ministry of Health, MIUR, the March of Dimes, Burroughs Wellcome Fund NINDS, NIH. Contract grant number: Ricerca Corrente 2008 to BD; Ricerca Finalizzata 2006 ex art. 56 to EMV; Telethon grant n. GGP08145 to EB/EMV.

Publisher Copyright:
© 2009, John Wiley and Sons Inc. All rights reserved.

Keywords

  • COACH syndrome
  • Congenital hepatic fibrosis
  • Joubert syndrome and related disorders
  • MKS3
  • TMEM67

Fingerprint Dive into the research topics of 'MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement'. Together they form a unique fingerprint.

Cite this