{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:58:21Z","timestamp":1740167901633,"version":"3.37.3"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T00:00:00Z","timestamp":1525996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1140450"],"award-info":[{"award-number":["1140450"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Cryptorchidism is one of the most common congenital disorders in boys, and several genetic, hormonal, and environmental factors have been proposed as possible causes for this genitourinary defect. Genetic factors have been intensively searched, but relatively few pathogenic variants have been described. Cryptorchidism is a frequent finding in patients with <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies, a group of syndrome caused by mutations in genes of the Ras\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway. Our aim was to determine whether patients with isolated cryptorchidism (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>) exhibit Ras\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway gene variants associated with <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies. Two hundred thirty\u2010nine patients with <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content> were recruited after orchidopexy. Determination of Ras\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway gene variants was performed by high\u2010resolution melting (<jats:styled-content style=\"fixed-case\">HRM<\/jats:styled-content>) analysis followed by sequencing. Restriction or allele\u2010specific amplification assay was applied to (i) variant confirmation; (ii) search in healthy controls; and (iii) segregation analysis. Controls correspond to 100 healthy Chilean adults without a history of cryptorchidism. Molecular analysis showed one synonymous substitution (<jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>_p.Q456Q) in two patients and four missense substitutions (<jats:styled-content style=\"fixed-case\">SOS<\/jats:styled-content>1_ p.R497Q, <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>_ p.F595L, <jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content>_ p.T50I, and <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>2K2_ p.Y134C) in five patients. Our results suggest that some patients with isolated cryptorchidism, but with no evidence of dysmorphic features suggestive of <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>opathies, may harbor Ras\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathway gene alterations.<\/jats:p>","DOI":"10.1111\/andr.12501","type":"journal-article","created":{"date-parts":[[2018,5,12]],"date-time":"2018-05-12T04:29:12Z","timestamp":1526099352000},"page":"579-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Study of Ras\/<scp>MAPK<\/scp> pathway gene variants in Chilean patients with Cryptorchidism"],"prefix":"10.1111","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0461-7393","authenticated-orcid":false,"given":"F.","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Vallejos","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Ponce","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Unanue","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. I.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"C\u00e9lis","sequence":"additional","affiliation":[{"name":"Pediatric Urology Department Hospital Cl\u00ednico San Borja \u2013 Arriar\u00e1n Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Arcos","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Belmar","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research School of Medicine University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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