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All families were subsequently analyzed for pathogenic copy number variants (CNVs) using CoverageMaster.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Novel pathogenic homozygous SNVs in known CHH genes were identified in four families: two families with variants in <jats:italic>GNRHR<\/jats:italic>, and two others harboring <jats:italic>KISS1R<\/jats:italic> variants. Subsequent investigation of CNVs in the remaining two families identified novel unique large deletions in <jats:italic>ANOS1<\/jats:italic>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>A combined, systematic analysis of single nucleotide and CNVs helps to improve the diagnostic yield for variants in patients with CHH.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-024-10598-3","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T13:02:43Z","timestamp":1723640563000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism"],"prefix":"10.1186","volume":"25","author":[{"given":"Yassine","family":"Zouaghi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anbreen Mazhar","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Irshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Adamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaleeq ur","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrin","family":"Fatima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nida","family":"Najmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"De Azevedo Correa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Habibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Boizot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas J.","family":"Niederl\u00e4nder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Santoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Acierno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Pitteloud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"issue":"4","key":"10598_CR1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/j.1399-0004.1986.tb00607.x","volume":"30","author":"G Filippi","year":"1986","unstructured":"Filippi G. 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Anonymized data was shared between the University of the Punjab (Lahore, Pakistan) and the Lausanne University Hospital (Lausanne, Switzerland) in the context of a registered study (clinicaltrials.gov, NCT01601171).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"787"}}