Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).
Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).
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DOI：
10.1136/jmg.2009.067249
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发表时间：
2010-01
影响因子：
4
通讯作者：
Glass IA
中科院分区：
文献类型：
--
作者：
Doherty D;Parisi MA;Finn LS;Gunay-Aygun M;Al-Mateen M;Bates D;Clericuzio C;Demir H;Dorschner M;van Essen AJ;Gahl WA;Gentile M;Gorden NT;Hikida A;Knutzen D;Ozyurek H;Phelps I;Rosenthal P;Verloes A;Weigand H;Chance PF;Dobyns WB;Glass IA
为了确定COACH综合征的遗传原因，COACH综合征是一种罕见的常染色体隐性遗传疾病，其特征是小脑蚓部发育不全、智力低下（发育迟缓/智力低下）、共济失调、缺损和肝纤维化。小脑蚓部发育不全福尔斯属于一种称为臼齿征（MTS）的中后脑畸形，使COACH成为Joubert综合征相关疾病（JSRD）。在251个JSRD家族的队列中，23个家族中的26名受试者符合COACH综合征的标准，COACH综合征定义为JSRD加上临床明显的肝病。JSRD的诊断标准是临床表现（智力障碍、张力减退、共济失调）加上支持性脑成像结果（MTS或小脑蚓部发育不全）。在所有DNA可用的受试者中对MKS 3/TMEM 67进行测序。在没有MKS 3突变的COACH受试者中，还对CC 2D 2A、RPGRIP 1 L和CEP 290进行了测序。19/23个患有COACH综合征的家族（83%）携带MKS 3突变，而2/209（1%）患有JSRD但无肝病。另外两个COACH家族携带CC 2D 2A突变，一个家族携带RPGRIP 1 L突变，一个家族缺乏MKS 3、CC 2D 2A、RPGRIP 1 L和CEP 290突变。来自三名受试者的肝活检，每一个都有三个基因之一的突变，揭示了先天性肝纤维化/导管板畸形谱内的变化。在有和没有肝脏疾病的JSRD中，MKS 3突变占21/232个家族（9%）。MKS 3突变是大多数COACH综合征的原因，CC 2D 2A和RPGRIP 1 L的贡献较小;因此，MKS 3应该是JSRD合并肝病和/或缺损患者中检测的第一个基因，其次是CC 2D 2A和RPGRIP 1 L。
To identify genetic causes of COACH syndrome COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L.
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影响因子：
9.8
作者：
Gorden, Nicholas T.;Arts, Heleen H.;Doherty, Dan
通讯作者：
Doherty, Dan
影响因子：
2
作者：
Braddock, Stephen R.;Henley, Kimberly M.;Maria, Bernard L.
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影响因子：
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作者：
Frank, Valeska;Bruechle, Nadina Ortiz;Bergman, Carsten
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影响因子：
3.9
作者：
Brancati, Francesco;Iannicelli, Miriam;Travaglini, Lorena;Mazzotta, Annalisa;Bertini, Enrico;Boltshauser, Eugen;D'Arrigo, Stefano;Emma, Francesco;Fazzi, Elisa;Gallizzi, Romina;Gentile, Mattia;Loncarevic, Damir;Mejaski-Bosnjak, Vlatka;Pantaleoni, Chiara;Rigoli, Luciana;Salpietro, Carmelo D.;Signorini, Sabrina;Stringini, Gilda Rita;Verloes, Alain;Zabloka, Dominika;Dallapiccola, Bruno;Gleeson, Joseph G.;Valente, Enza Maria
通讯作者：
Valente, Enza Maria
影响因子：
1.4
作者：
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通讯作者：
Pascotto, A