{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T09:45:54Z","timestamp":1779270354792,"version":"3.51.4"},"reference-count":101,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T00:00:00Z","timestamp":1525737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD30428"],"award-info":[{"award-number":["R01HD30428"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital Hypopituitarism is caused by genetic and environmental factors. Over 30 genes have been implicated in isolated and\/or combined pituitary hormone deficiency. The etiology remains unknown for up to 80% of the patients, but most cases have been analyzed by limited candidate gene screening. Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">PROP<\/jats:styled-content>1<\/jats:italic> gene are the most common known cause, and the frequency of mutations in this gene varies greatly by ethnicity. We designed a custom array to assess the frequency of mutations in known hypopituitarism genes and new candidates, using single molecule molecular inversion probes sequencing (sm<jats:styled-content style=\"fixed-case\">MIPS<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used this panel for the first systematic screening for causes of hypopituitarism in children. Molecular inversion probes were designed to capture 693 coding exons of 30 known genes and 37 candidate genes. We captured genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> from 51 pediatric patients with <jats:styled-content style=\"fixed-case\">CPHD<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a043) or isolated <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> deficiency (<jats:styled-content style=\"fixed-case\">IGHD<\/jats:styled-content>) (<jats:italic>n<\/jats:italic>\u00a0=\u00a08) and their parents and conducted next generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We obtained deep coverage over targeted regions and demonstrated accurate variant detection by comparison to whole\u2010genome sequencing in a control individual. We found a dominant mutation <jats:italic><jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content>1<\/jats:italic>, p.R209H, in a three\u2010generation pedigree with <jats:styled-content style=\"fixed-case\">IGHD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>sm<jats:styled-content style=\"fixed-case\">MIPS<\/jats:styled-content> is an efficient and inexpensive method to detect mutations in patients with hypopituitarism, drastically limiting the need for screening individual genes by Sanger sequencing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.395","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T23:34:42Z","timestamp":1525822482000},"page":"514-525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Next generation sequencing panel based on single molecule molecular inversion probes for detecting genetic variants 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