{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T04:06:04Z","timestamp":1747109164948,"version":"3.40.5"},"reference-count":25,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173517","81974111","81800762","82000366"],"award-info":[{"award-number":["82173517","81974111","81800762","82000366"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Global Medical Genetics"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.gmg.2025.100037","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T19:45:24Z","timestamp":1737229524000},"page":"100037","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["PROKR2 mutations and SPRY4 variants with uncertain significance in a Kallmann syndrome family: Incomplete penetrance"],"prefix":"10.1016","volume":"12","author":[{"given":"Yuanfan","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiehan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianshu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.gmg.2025.100037_bib1","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1210\/er.2018-00116","article-title":"Clinical management of congenital hypogonadotropic hypogonadism","volume":"40","author":"Young","year":"2019","journal-title":"Endocr. Rev."},{"issue":"2","key":"10.1016\/j.gmg.2025.100037_bib2","article-title":"A case of novel mutation in ANOS1 (KAL1) gene and review of Kallmann syndrome","volume":"2023","author":"Arora","year":"2023","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"10.1016\/j.gmg.2025.100037_bib3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.metabol.2017.10.012","article-title":"Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism","volume":"86","author":"Stamou","year":"2018","journal-title":"Metabolism"},{"issue":"34","key":"10.1016\/j.gmg.2025.100037_bib4","doi-asserted-by":"crossref","first-page":"15140","DOI":"10.1073\/pnas.1009622107","article-title":"Oligogenic basis of isolated gonadotropin-releasing hormone deficiency","volume":"107","author":"Sykiotis","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"10","key":"10.1016\/j.gmg.2025.100037_bib5","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1093\/humrep\/deaa185","article-title":"GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty","volume":"35","author":"Mosbah","year":"2020","journal-title":"Hum. Reprod."},{"issue":"5","key":"10.1016\/j.gmg.2025.100037_bib6","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1210\/clinem\/dgaa052","article-title":"Serum anti-mullerian hormone in the prediction of response to hCG stimulation in children With DSD","volume":"105","author":"Lucas-Herald","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"6","key":"10.1016\/j.gmg.2025.100037_bib7","doi-asserted-by":"crossref","DOI":"10.3390\/genes13061012","article-title":"Molecular cytogenetics reveals mosaicism in human umbilical vein endothelial cells","volume":"13","author":"Binz","year":"2022","journal-title":"Genes (Basel)"},{"issue":"1","key":"10.1016\/j.gmg.2025.100037_bib8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12920-022-01205-z","article-title":"Compound heterozygous variants in DYNC2H1 in a foetus with type III short rib-polydactyly syndrome and situs inversus totalis","volume":"15","author":"Cheng","year":"2022","journal-title":"BMC Med Genom."},{"issue":"8","key":"10.1016\/j.gmg.2025.100037_bib9","article-title":"Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism","author":"Malone","year":"2019","journal-title":"Elife"},{"issue":"5","key":"10.1016\/j.gmg.2025.100037_bib10","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ajhg.2013.04.008","article-title":"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism","volume":"92","author":"Miraoui","year":"2013","journal-title":"Am. J. Hum. Genet"},{"issue":"3","key":"10.1016\/j.gmg.2025.100037_bib11","doi-asserted-by":"crossref","first-page":"192","DOI":"10.6065\/apem.1938148.074","article-title":"Dizygotic twin sisters with normosmic idiopathic hypogonadotropic hypogonadism caused by an FGFR1 gene variant","volume":"25","author":"Choe","year":"2020","journal-title":"Ann. Pedia Endocrinol. Metab."},{"issue":"1","key":"10.1016\/j.gmg.2025.100037_bib12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s00439-020-02147-1","article-title":"Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease","volume":"140","author":"Cangiano","year":"2021","journal-title":"Hum. Genet"},{"issue":"3","key":"10.1016\/j.gmg.2025.100037_bib13","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1096\/fj.201801575R","article-title":"PROKR2 mutations in idiopathic hypogonadotropic hypogonadism: selective disruption of the binding to a Galpha-protein leads to biased signaling","volume":"33","author":"Zhao","year":"2019","journal-title":"FASEB J."},{"issue":"6","key":"10.1016\/j.gmg.2025.100037_bib14","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/cen.14822","article-title":"Genetic spectrum of Kallmann syndrome: single-center experience and systematic review","volume":"97","author":"Patil","year":"2022","journal-title":"Clin. Endocrinol. (Oxf. )"},{"issue":"3","key":"10.1016\/j.gmg.2025.100037_bib15","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.fertnstert.2012.11.003","article-title":"PROKR2 mutations in autosomal recessive Kallmann syndrome","volume":"99","author":"Tommiska","year":"2013","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.gmg.2025.100037_bib16","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3389\/fendo.2019.00781","article-title":"A rare SPRY4 gene mutation is associated with anosmia and adult-onset isolated hypogonadotropic hypogonadism","volume":"10","author":"Indirli","year":"2019","journal-title":"Front Endocrinol. (Lausanne)"},{"issue":"6","key":"10.1016\/j.gmg.2025.100037_bib17","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s43032-021-00638-8","article-title":"Advances in genetic diagnosis of kallmann syndrome and genetic interruption","volume":"29","author":"Liu","year":"2022","journal-title":"Reprod. Sci."},{"key":"10.1016\/j.gmg.2025.100037_bib18","doi-asserted-by":"crossref","unstructured":"Hardelin J.P., Dode C. The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sex Dev. 2008;2(4\u20135):181\u2013193. doi:10.1159\/000152034.","DOI":"10.1159\/000152034"},{"key":"10.1016\/j.gmg.2025.100037_bib19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000312698","article-title":"Kallmann syndrome caused by mutations in the PROK2 and PROKR2 genes: pathophysiology and genotype-phenotype correlations","volume":"39","author":"Sarfati","year":"2010","journal-title":"Front Horm. Res"},{"key":"10.1016\/j.gmg.2025.100037_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2021.665174","article-title":"Oligogenic inheritance underlying incomplete penetrance of PROKR2 mutations in hypogonadotropic hypogonadism","volume":"12","author":"Mkaouar","year":"2021","journal-title":"Front Genet"},{"key":"10.1016\/j.gmg.2025.100037_bib21","article-title":"A novel noncanonical splicing mutation of ANOS1 gene in siblings with kallmann syndrome identified by whole-exome sequencing","author":"Xia","year":"2021","journal-title":"Reprod. Sci."},{"issue":"1","key":"10.1016\/j.gmg.2025.100037_bib22","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1542\/peds.2018-1099E","article-title":"Genomic sequencing expansion and incomplete penetrance","volume":"143","author":"Shieh","year":"2019","journal-title":"Pediatrics"},{"issue":"9","key":"10.1016\/j.gmg.2025.100037_bib23","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrendo.2015.112","article-title":"Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment","volume":"11","author":"Boehm","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"issue":"7","key":"10.1016\/j.gmg.2025.100037_bib24","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.acra.2011.02.018","article-title":"Reproducibility and repeatability of volumetric measurements for olfactory bulb volumetry: which method is appropriate? An update using 3 Tesla MRI","volume":"18","author":"Burmeister","year":"2011","journal-title":"Acad. Radio."},{"issue":"1","key":"10.1016\/j.gmg.2025.100037_bib25","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/cge.12697","article-title":"Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome","volume":"90","author":"Braun","year":"2016","journal-title":"Clin. Genet"}],"container-title":["Global Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2699940425000384?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2699940425000384?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T16:38:48Z","timestamp":1747067928000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2699940425000384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["S2699940425000384"],"URL":"https:\/\/doi.org\/10.1016\/j.gmg.2025.100037","relation":{},"ISSN":["2699-9404"],"issn-type":[{"type":"print","value":"2699-9404"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PROKR2 mutations and SPRY4 variants with uncertain significance in a Kallmann syndrome family: Incomplete penetrance","name":"articletitle","label":"Article Title"},{"value":"Global Medical Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gmg.2025.100037","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.","name":"copyright","label":"Copyright"}],"article-number":"100037"}}