{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:56:52Z","timestamp":1790081812358,"version":"4.0.1"},"reference-count":33,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2009,2,3]]},"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by <jats:italic>ZIC3<\/jats:italic> mutations, the <jats:italic>ZIC3<\/jats:italic> coding region was sequenced.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In a patient with the VACTERL association a 6-nucleotide insertion was found in the GCC repeat of the <jats:italic>ZIC3<\/jats:italic> gene, which is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. The polyalanine expansion is a novel <jats:italic>ZIC3<\/jats:italic> mutation which was not found in 336 chromosomes from 192 ethnically matched controls. The mutation was also not present in the mother, suggesting it occurred de novo in the patient and is therefore a pathogenetic mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>It is hypothesized that this novel and de novo polyalanine expansion in <jats:italic>ZIC3<\/jats:italic> contributes to the VACTERL association in this patient.<\/jats:p>\n                  <jats:p>A newborn male is described with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of the VACTERL association overlaps with X-linked heterotaxy caused by <jats:italic>ZIC3<\/jats:italic> mutations, the <jats:italic>ZIC3<\/jats:italic> coding region was sequenced, and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the <jats:italic>ZIC3<\/jats:italic> gene contributes to the VACTERL association in this patient.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.060913","type":"journal-article","created":{"date-parts":[[2010,5,7]],"date-time":"2010-05-07T04:43:52Z","timestamp":1273207432000},"page":"351-355","source":"Crossref","is-referenced-by-count":69,"title":["Polyalanine expansion in the <i>ZIC3<\/i> gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?"],"prefix":"10.1136","volume":"47","author":[{"given":"Marja 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