{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:43:27Z","timestamp":1785577407756,"version":"3.56.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"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":["Clinical Endocrinology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To study phenotype\u2010genotype data of Asian\u2212Indian Kallmann syndrome (KS) from our center and systematically review the studies analyzing multiple congenital hypogonadotropic hypogonadism (CHH) genes in KS cohorts using next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Patients, Measurement<\/jats:title><jats:p>Five hundred twenty\u2010two\u00a0KS probands (our center <jats:italic>n<\/jats:italic>\u2009=\u200978, published studies <jats:italic>n<\/jats:italic>\u2009=\u2009444) were included in this systematic review. Molecular diagnosis was considered if the likely pathogenic\/pathogenic variant in known CHH gene\/s was reported in the appropriate allelic state. Varsome prediction tool (following American College of Medical Genetics standards) was used to analyze the variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>For our center, the molecular diagnosis was seen in 20.5% of probands and was seen more often with severe than partial reproductive phenotype (28.3% vs. 4%, <jats:italic>p<\/jats:italic>\u2009=\u2009.0013). Our center data adds eight novel variants. The molecular diagnosis was seen in 31% as per the systematic review and analysis. It ranged from 16.6% to 72.2% at different centers. The affected genes were <jats:italic>FGFR1<\/jats:italic> (9.8%), <jats:italic>ANOS1<\/jats:italic> (7.5%), <jats:italic>PROKR2<\/jats:italic> (6.1%), <jats:italic>CHD7<\/jats:italic> (5.4%), oligogenic (2.1%), and others &lt;1% each (<jats:italic>FGF8, SOX10, PROK2, SEMA3A, IL17RD<\/jats:italic>, and\u00a0<jats:italic>GNRHR<\/jats:italic>). <jats:italic>FGFR1 and ANOS1<\/jats:italic> were the commonly affected genes globally, whereas <jats:italic>PROKR2<\/jats:italic> was commonest in studies from China and <jats:italic>CHD7<\/jats:italic> from Japan, South Korea and Poland.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion(s)<\/jats:title><jats:p>This systematic review highlights that the genetic yield is 31% in KS probands, with distinct regional variations. The association of severe reproductive phenotype with the higher genetic yield needs further validation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14822","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T03:09:57Z","timestamp":1663902597000},"page":"804-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic spectrum of Kallmann syndrome: Single\u2010center experience and systematic review"],"prefix":"10.1111","volume":"97","author":[{"given":"Virendra A.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Endocrinology Seth G S Medical College and KEM Hospital Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-4471","authenticated-orcid":false,"given":"Anurag Ranjan","family":"Lila","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Seth G S Medical 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