{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:50Z","timestamp":1787014010001,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010787","name":"Genome Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","award":["OGI\u2010147"],"award-info":[{"award-number":["OGI\u2010147"]}],"id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Exome sequencing (ES) is an effective diagnostic tool with a high yield in consanguineous families. However, how diagnostic yield and mode of inheritance relate to family structure has not been well delineated. We reviewed ES results from families enrolled in the Care4Rare Canada research consortium with various degrees of consanguinity. We contrasted the diagnostic yield in families with parents who are second cousins or closer (\u201cclose\u201d consanguinity) vs those more distantly related or from isolated populations (\u201cpresumed\u201d consanguinity). We further stratified by number of affected individuals (multiple affected [\u201cmultiplex\u201d] vs single affected [simplex]). The overall yield in 116 families was 45.7% (n = 53) with no significant difference between subgroups. Homozygous variants accounted for 100% and 75% of diagnoses in close and presumed consanguineous multiplex families, respectively. In simplex presumed consanguineous families, a striking 46.2% of diagnoses were due to de novo variants, vs only 11.8% in simplex closely consanguineous families (88.2% homozygous). Our data underscores the high yield of ES in consanguineous families and highlights that while a singleton approach may frequently be reasonable and a responsible use of resources, trio sequencing should be strongly considered in simplex families in the absence of confirmed consanguinity given the proportion of de novo variants.<\/jats:p>","DOI":"10.1111\/cge.13736","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T01:02:25Z","timestamp":1583974945000},"page":"835-843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["When to think outside the autozygome: Best practices for exome sequencing in \u201cconsanguineous\u201d families"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-0429","authenticated-orcid":false,"given":"Alison","family":"Eaton","sequence":"first","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taila","family":"Hartley","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Kernohan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"},{"name":"Newborn Screening Ontario Children's Hospital of Eastern Ontario  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Ito","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Lamont","sequence":"additional","affiliation":[{"name":"Alberta Children's Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Parboosingh","sequence":"additional","affiliation":[{"name":"Alberta Children's Hospital Research Institute, Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Barrowman","sequence":"additional","affiliation":[{"name":"Clinical Research Unit, Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Care4Rare consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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