{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:20:26Z","timestamp":1790680826001,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aetiology of Mayer\u2013Rokitansky\u2013K\u00fcster\u2013Hauser (MRKH) syndrome, characterized by uterovaginal agenesis in 46,XX women, remains poorly understood. Since familial occurrences are rare, genetic findings reported so far only apply to a minority of mainly sporadic cases and most studies have not included other family members enabling segregation analysis. Herein, we report on the investigation of a unique three-generation family of two female cousins with MRKH syndrome and unilateral renal agenesis (RA) and two deceased male relatives with RA. We performed whole-exome sequencing (WES) in eight family members leading to the identification of a novel pathogenic (CADD\u2009=\u200933) c.705G&gt;T missense variant in GREB1L, a gene recently identified as a novel cause of RA. Previous reports include several cases of female fetuses with bilateral RA and uterus agenesis, which support GREB1L as an important gene in both kidney and female genital tract development. The pedigree is compatible with autosomal dominant inheritance with incomplete penetrance following a parent-origin-specific manner, which could be due to imprinting. To our knowledge, this is the first investigation of a larger MRKH syndrome pedigree using WES, and we suggest GREB1L as a novel and promising candidate gene in the aetiology of MRKH syndrome.<\/jats:p>","DOI":"10.1093\/humrep\/dez126","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:35:17Z","timestamp":1561487717000},"page":"1838-1846","source":"Crossref","is-referenced-by-count":53,"title":["Whole-exome sequencing identifies a GREB1L variant in a three-generation family with M\u00fcllerian and renal agenesis: a novel candidate gene in Mayer\u2013Rokitansky\u2013K\u00fcster\u2013Hauser (MRKH) syndrome. A case report"],"prefix":"10.1093","volume":"34","author":[{"given":"Morten K","family":"Herlin","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Aalborg University Hospital, Ladeg\u00e5rdsgade 5, bygning E, 5. Sal, 9000 Aalborg, Denmark"},{"name":"Pediatrics and Adolescent Medicine, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vang Q","family":"Le","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan T","family":"H\u00f8jland","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Aalborg University Hospital, Ladeg\u00e5rdsgade 5, bygning E, 5. Sal, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Ernst","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Okkels","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid C","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aalborg University Hospital, Ladeg\u00e5rdsgade 3, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Aalborg University Hospital, Ladeg\u00e5rdsgade 5, bygning E, 5. Sal, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge S","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"2019112610311659000_ref1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1750-1172-4-25","article-title":"Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports","volume":"4","author":"Bernardini","year":"2009","journal-title":"Orphanet J Rare Dis"},{"key":"2019112610311659000_ref2","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1056\/NEJMoa040533","article-title":"A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman","volume":"351","author":"Biason-Lauber","year":"2004","journal-title":"N Engl J Med"},{"key":"2019112610311659000_ref3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1534\/genetics.117.1125","article-title":"A gene implicated in activation of retinoic acid receptor 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