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

被引：83

作者：

Brancati, Francesco ^{[2
,3
]}

Iannicelli, Miriam ^{[4
]}

Travaglini, Lorena ^{[4
]}

Mazzotta, Annalisa

Bertini, Enrico ^{[11
]}

Boltshauser, Eugen ^{[12
]}

D'Arrigo, Stefano ^{[7
]}

Emma, Francesco ^{[5
]}

Fazzi, Elisa ^{[6
]}

Gallizzi, Romina ^{[8
]}

Gentile, Mattia ^{[10
]}

Loncarevic, Damir ^{[9
]}

Mejaski-Bosnjak, Vlatka ^{[9
]}

Pantaleoni, Chiara ^{[7
]}

Rigoli, Luciana ^{[8
]}

Salpietro, Carmelo D. ^{[8
]}

Signorini, Sabrina ^{[6
]}

Stringini, Gilda Rita ^{[5
]}

Verloes, Alain ^{[13
]}

Zabloka, Dominika ^{[14
]}

Dallapiccola, Bruno ^{[4
]}

Gleeson, Joseph G. ^{[4
]}

Valente, Enza Maria

机构：

[1] CSS Mendel Inst, Neurogenet Unit, IRCCS, I-00198 Rome, Italy

[2] G Annunzio Univ Fdn, Dept Biomed Sci, Chieti, Italy

[3] G Annunzio Univ Fdn, Aging Res Ctr, CeSI, Chieti, Italy

[4] Sapienza Univ, Dept Expt Med, Rome, Italy

[5] IRCCS Bambino Gesu Hosp, Dept Nephrol, Rome, Italy

[6] Univ Pavia, Dept Child Neurol & Psychiat, IRCCS C Mondino Fdn, I-27100 Pavia, Italy

[7] Carlo Besta Neurol Inst Fdn, Div Neurol Sviluppo, Milan, Italy

[8] Univ Messina, Dept Med & Surg Pediat Sci, Messina, Italy

[9] Childrens Hosp Zagreb, Dept Neuropediat, Zagreb, Croatia

[10] IRCCS Saverio De Bellis Hosp, Castellana Grotte, Italy

[11] IRCCS Bambino Gesu Hosp, Dept Lab Med, Rome, Italy

[12] Childrens Univ Hosp, Dept Neurol, Zurich, Switzerland

[13] Hop Robert Debre, F-75019 Paris, France

[14] Univ Calif San Diego, Dept Neurosci, Neurogenet Lab, La Jolla, CA 92093 USA

来源：

HUMAN MUTATION | 2009年 / 30卷 / 02期

关键词：

COACH syndrome; MKS3; TMEM67; Joubert syndrome and related disorders; congenital hepatic fibrosis; MECKEL-GRUBER-SYNDROME; CONGENITAL ATAXIA; HEPATIC-FIBROSIS; PRIMARY CILIUM; DUCTAL PLATE; GENE; OLIGOPHRENIA; COLOBOMA; MKS3;

D O I：

10.1002/humu.20924

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (C) 2008 Wiley-Liss, Inc.

引用

页码：E432 / E442

页数：11

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