{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:30:44Z","timestamp":1762543844879,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Argentino Sectorial (FONARSEC, Argentina)","award":["FS-BIO 05\/2017","PICT-A Cat.III 73\/2021"],"award-info":[{"award-number":["FS-BIO 05\/2017","PICT-A Cat.III 73\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our aim is to report a case of a patient with 46,XY DSDs in whom the identification of a novel variant in MYRF led to the detection of a clinically inapparent congenital heart defect. A full-term newborn presented with ambiguous genitalia, as follows: a 2 cm phallus, penoscrotal hypospadias, partially fused labioscrotal folds, an anogenital distance of 1.2 cm, and non-palpable gonads. The karyotype was 46,XY, serum testosterone and AMH were low, whereas LH and FSH were high, leading to the diagnosis of dysgenetic DSD. Whole exome sequencing identified a novel, heterozygous, nonsense variant in MYRF, classified as pathogenic according to the ACMG criteria. MYRF encodes a membrane-bound transcriptional factor expressed in several tissues associated with OCUGS syndrome (ophthalmic, cardiac, and urogenital anomalies). In the patient, oriented clinical assessment ruled out ophthalmic defects, but ultrasonography confirmed meso\/dextrocardia. We report a novel MYRF variant in a patient with 46,XY DSDs, allowing us to identify a clinically inapparent congenital heart defect by reverse phenotyping.<\/jats:p>","DOI":"10.3390\/jpm13071158","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:20:14Z","timestamp":1689801614000},"page":"1158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-1988","authenticated-orcid":false,"given":"Lourdes","family":"Correa Brito","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina P.","family":"Grinspon","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimena","family":"Lopez Dacal","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-6034","authenticated-orcid":false,"given":"Paula","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"},{"name":"Unidad de Medicina Traslacional, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Esnaola Azcoiti","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"},{"name":"Unidad de Medicina Traslacional, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agust\u00edn","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"},{"name":"Unidad de Medicina Traslacional, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Gabriela","family":"Ropelato","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"},{"name":"Unidad de Medicina Traslacional, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires C1425EFD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-3843","authenticated-orcid":false,"given":"Rodolfo A.","family":"Rey","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Endocrinol\u00f3gicas \u201cDr. C\u00e9sar Bergad\u00e1\u201d (CEDIE), CONICET\u2013FEI\u2013Divisi\u00f3n de Endocrinolog\u00eda, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Gallo 1330, Buenos Aires C1425EFD, Argentina"},{"name":"Unidad de Medicina Traslacional, Hospital de Ni\u00f1os Ricardo Guti\u00e9rrez, Buenos Aires C1425EFD, Argentina"},{"name":"Departamento de Histolog\u00eda, Biolog\u00eda Celular, Embriolog\u00eda y Gen\u00e9tica Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3389\/fendo.2020.00211","article-title":"Male Hypogonadism and Disorders of Sex Development","volume":"11","author":"Grinspon","year":"2020","journal-title":"Front. 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A"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:14:52Z","timestamp":1760127292000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/7\/1158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["jpm13071158"],"URL":"https:\/\/doi.org\/10.3390\/jpm13071158","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2023,7,19]]}}}