{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T09:40:43Z","timestamp":1698831643776},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,7]],"date-time":"2012-02-07T00:00:00Z","timestamp":1328572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Context\u2002<\/jats:bold> Mutations in the <jats:italic>GH1<\/jats:italic> gene have been identified in patients with isolated growth hormone deficiency (IGHD). Mutations causing aberrant splicing of exon 3 of <jats:italic>GH1<\/jats:italic> that have been identified in IGHD are inherited in an autosomal dominant manner, whereas other mutations in <jats:italic>GH1<\/jats:italic> that have been identified in IGHD are inherited in an autosomal recessive manner.<\/jats:p><jats:p><jats:bold>Objective\u2002<\/jats:bold> Two siblings born from nonconsanguineous healthy parents exhibited IGHD. To elucidate the cause, <jats:italic>GH1<\/jats:italic> in all family members was analysed.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Two novel mutations in <jats:italic>GH1<\/jats:italic>, a point mutation in intron 3 and a 16\u2010bp deletion in exon 3, were identified by sequence analyses. The intronic mutation was present in both siblings and was predicted to cause aberrant splicing. The deletion was present in one of the siblings as well as the mother with normal stature and was predicted to cause rapid degradation of mRNA through nonsense\u2010mediated mRNA decay. The point mutation was not identified in the parents\u2019 peripheral blood DNA; however, it was detected in the DNA extracted from the father\u2019s sperms. As a trace of the mutant allele was detected in the peripheral blood of the father using PCR\u2010RFLP, the mutation is likely to have occurred <jats:italic>de novo<\/jats:italic> at an early developmental stage before differentiation of somatic cells and germline cells.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> This is the first report of mosaicism for a mutation in <jats:italic>GH1<\/jats:italic> in a family with IGHD. It is clear that the intronic mutation plays a dominant role in the pathogenesis of IGHD in this family, as one of the siblings who had only the point mutation was affected. On the other hand, the other sibling was a compound heterozygote for the point mutation and the 16\u2010bp deletion and it may be arguable whether IGHD in this patient should be regarded as autosomal dominant or recessive.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2011.04224.x","type":"journal-article","created":{"date-parts":[[2011,9,21]],"date-time":"2011-09-21T07:45:42Z","timestamp":1316591142000},"page":"420-424","source":"Crossref","is-referenced-by-count":6,"title":["Isolated growth hormone deficiency in two siblings because of paternal mosaicism for a mutation in the <i>GH1<\/i> gene"],"prefix":"10.1111","volume":"76","author":[{"given":"Mayuko","family":"Tsubahara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitaka","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin\u2010ichi","family":"Niijima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiyo","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kamijo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiharu","family":"Murata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Haruna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihisa","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,2,7]]},"reference":[{"issue":"3","key":"e_1_2_6_2_2","first-page":"480","article-title":"GH1 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