{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:30:26Z","timestamp":1791286226927,"version":"4.1.0"},"reference-count":75,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify genetic causes of COACH syndrome<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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). <jats:italic>MKS3<\/jats:italic>\/<jats:italic>TMEM67<\/jats:italic> was sequenced in all subjects for whom DNA was available. In COACH subjects without <jats:italic>MKS3<\/jats:italic> mutations, <jats:italic>CC2D2A<\/jats:italic>, <jats:italic>RPGRIP1L<\/jats:italic> and <jats:italic>CEP290<\/jats:italic> were also sequenced.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>19\/23 families (83%) with COACH syndrome carried <jats:italic>MKS3<\/jats:italic> mutations, compared to 2\/209 (1%) with JSRD but no liver disease. Two other families with COACH carried <jats:italic>CC2D2A<\/jats:italic> mutations, one family carried <jats:italic>RPGRIP1L<\/jats:italic> mutations, and one lacked mutations in <jats:italic>MKS3<\/jats:italic>, <jats:italic>CC2D2A<\/jats:italic>, <jats:italic>RPGRIP1L<\/jats:italic> and <jats:italic>CEP290<\/jats:italic>. 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, <jats:italic>MKS3<\/jats:italic> mutations account for 21\/232 families (9%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mutations in <jats:italic>MKS3<\/jats:italic> are responsible for the majority of COACH syndrome, with minor contributions from <jats:italic>CC2D2A<\/jats:italic> and <jats:italic>RPGRIP1L<\/jats:italic>; therefore, <jats:italic>MKS3<\/jats:italic> should be the first gene tested in patients with JSRD plus liver disease and\/or coloboma, followed by <jats:italic>CC2D2A<\/jats:italic> and <jats:italic>RPGRIP1L<\/jats:italic>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.067249","type":"journal-article","created":{"date-parts":[[2009,7,2]],"date-time":"2009-07-02T20:25:46Z","timestamp":1246566346000},"page":"8-21","source":"Crossref","is-referenced-by-count":128,"title":["Mutations in 3 genes 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