{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:00:26Z","timestamp":1773424826826,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,6]],"date-time":"2019-10-06T00:00:00Z","timestamp":1570320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Desbuquois dysplasia (DBQD1 [MIM 251450]) is an autosomal recessive chondrodysplasia with micromelia, severe joint laxity and dislocations, and a characteristic radiographic \u201cmonkey wrench\u201d appearance at the proximal femur. Type 1 Desbuquois dysplasia is caused by mutations in <jats:italic>CANT1<\/jats:italic> and is distinct from Type 2, caused by mutations in <jats:italic>XYLT1<\/jats:italic>, in that the former has unique hand anomalies including accessory phalangeal ossification centers, advanced carpal bone maturation, and\/or axial phalangeal deviation. Severe prenatal presentations have been rarely reported. We report a Pakistani female in a consanguineous relationship with a diagnosis of Type 1 Desbuquois dysplasia in three consecutive pregnancies. Multiple similar severe fetal limb anomalies were detected by ultrasound in Pregnancy 1 and 2. Regions of homozygosity within the single nucleotide polymorphism (SNP)\u2010microarray from both terminated fetuses were compared, revealing <jats:italic>CANT1<\/jats:italic> as a likely disease\u2010causing candidate gene. Insufficient fetal DNA precluded confirmatory testing, therefore parents were tested; both had a previously reported heterozygous <jats:italic>CANT1<\/jats:italic> mutation (c.643G&gt;T; Glu215Term). The patient presented with a third pregnancy revealing similarly abnormal limb position and probable polysyndactyly by ultrasound. Targeted testing of <jats:italic>CANT1<\/jats:italic> revealed homozygous c.643G&gt;T <jats:italic>CANT1<\/jats:italic> mutations and this pregnancy was terminated. In clinical situations in which ample DNA is not available or more expensive testing (e.g., whole exome sequencing) with a longer turnaround time is not feasible, utilization of SNP\u2010microarray in consanguineous families at risk for rare autosomal recessive disorders may dramatically narrow the list of candidate genes.<\/jats:p>","DOI":"10.1002\/ajmg.a.61372","type":"journal-article","created":{"date-parts":[[2019,10,6]],"date-time":"2019-10-06T08:59:25Z","timestamp":1570352365000},"page":"2490-2493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prenatal diagnosis of Desbuquois dysplasia Type 1: Utilization of high\u2010density SNP array to map homozygosity and identify the gene"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-6088","authenticated-orcid":false,"given":"Katherine R.","family":"Forster","sequence":"first","affiliation":[{"name":"Johns Hopkins Center for Fetal Therapy, Department of Gynecology and Obstetrics Johns Hopkins University  Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jody E.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University  Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin J.","family":"Blakemore","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine, Department of Gynecology and Obstetrics, McKusick\u2010Nathans Institute of the Department of Genetic Medicine Johns Hopkins University  Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet A.","family":"Baschat","sequence":"additional","affiliation":[{"name":"Johns Hopkins Center for Fetal Therapy, Department of Gynecology and Obstetrics Johns Hopkins University  Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-5626","authenticated-orcid":false,"given":"Julie","family":"Hoover\u2010Fong","sequence":"additional","affiliation":[{"name":"Greenberg Center for Skeletal Dysplasias, McKusick\u2010Nathans Institute of the Department of Genetic Medicine, Department of Pediatrics Johns Hopkins University  Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181ceb95d"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-201312000-00042"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33264"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.020"},{"key":"e_1_2_5_6_1","first-page":"573","article-title":"Nanisme chondrodystrophique avec 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