{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:30:59Z","timestamp":1790767859679,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 1723\/4\u20101"],"award-info":[{"award-number":["RE 1723\/4\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK076683"],"award-info":[{"award-number":["DK076683"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The VATER\/VACTERL association refers to the nonrandom co\u2010occurrence of at least three of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). Patients presenting with two CFs have been termed VATER\/VACTERL\u2010like phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We surveyed the exome for recessive disease variants in three affected sib\u2010pairs. Sib\u2010pair 971 consisted of two brothers with ARM and additional hydronephrosis in one brother. Sib\u2010pair 1098 consisted of two sisters with ARM. In family 1346, the daughter presented with ARM and additional hypoplasia of both small fingers and ankyloses. Her brother presented with unilateral isolated radial hypoplasia. Sib\u2010pairs 971 and 1346 resembled a VATER\/VACTERL\u2010like phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected a novel maternally inherited missense variant (c.1340G\u2009&gt;\u2009T) and a rare paternally inherited deletion of the trans\u2010allele in <jats:italic>HSPA6<\/jats:italic> in both siblings of family 1346. HSPA6 belongs to the heat shock protein (HSP) 70 family. Re\u2010sequencing of <jats:italic>HSPA6<\/jats:italic> in 167 patients with VATER\/VACTERL and VATER\/VACTERL\u2010like phenotypes did not reveal any additional bi\u2010allelic variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Until now, only TNF\u2010receptor associated protein 1 (<jats:italic>TRAP1<\/jats:italic>) had been reported as an autosomal recessive disease\u2010gene for the VATER\/VACTERL association. <jats:italic>TRAP1<\/jats:italic> belongs to the heat shock protein 90 family (HSP90). Both <jats:italic>Hsp70<\/jats:italic> and <jats:italic>Hsp90<\/jats:italic> genes have been shown to be important embryonic drivers in the formation of mouse embryonic forelimb tissue. Our results suggest <jats:italic>HSPA6<\/jats:italic> as a new candidate gene in VATER\/VACTERL\u2010like phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1493","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T23:14:44Z","timestamp":1553037284000},"page":"591-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<i>HSPA6<\/i>: A new autosomal recessive candidate gene for the VATER\/VACTERL malformation spectrum"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-8962","authenticated-orcid":false,"given":"Franziska","family":"Kause","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn  Bonn 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Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Altmueller","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics University of Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Herms","sequence":"additional","affiliation":[{"name":"Department of Genomics Life &amp; Brain Center  Bonn Germany"},{"name":"Institute of Medical Genetics and Pathology, University Hospital Basel  Basel Switzerland"},{"name":"Department of Biomedicine, Human Genomics Research Group University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina C.","family":"Hilger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn  Bonn Germany"},{"name":"Children's Hospital University of Bonn  Bonn 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