Published in

Wiley, Human Mutation: Variation, Informatics and Disease, 2(30), p. E432-E442, 2009

DOI: 10.1002/humu.20924

Links

Tools

Export citation

Search in Google Scholar

MKS3/TMEM67 Mutations Are a Major Cause of COACH Syndrome, a Joubert Syndrome Related Disorder with Liver Involvement

Journal article published in 2009 by P. de Lonlay, M. M. de Jong, Miriam Iannicelli, Annalisa Mazzotta, Francesco Brancati, Stefano D’Arrigo, Francesco Emma, P. Grattan Smith, Elisa Fazzi, Alain Verloes, Romina Gallizzi ORCID, Dominika Zabloka, A. Zankl, Enrico Bertini, Mattia Gentile ORCID and other authors.
This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

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. © 2008 Wiley-Liss, Inc.