{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:18:49Z","timestamp":1761718729987,"version":"3.37.3"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. <jats:italic><jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<\/jats:italic> is the main disease\u2010causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the mutation profile of genes related in three Chinese families with congenital aniridia through targeted sequencing technology. And we validated the candidate variants by <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\u2010based Sanger sequencing. Different degree impairments of islet function were observed in the patients with aniridia by carbohydrate tolerance butter and insulin release tests in our study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified four novel mutations of <jats:italic><jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<\/jats:italic> from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880del<jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content> (p.S294Cfs*46) and c.1124C&gt;G (p.P375R) in Family 1 with three patients, heterozygous frameshift mutation c.308delG (p.P103Qfs*21) in Family 2 with one patient, and c.1192delT (p.S398Pfs*126) in Family 3 with two patients. The three frameshift mutations of <jats:italic><jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<\/jats:italic> are co\u2010segregated with the aniridia from controls in the families, but the novel missense mutation is not co\u2010segregated with the phenotype. The frameshift mutations in Family 1 and Family 2 have effects to truncate the protein, but the frameshift mutation in Family 3 will prolong it. We confirmed the phenomenon of male gonadal mosaicism of <jats:italic><jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<\/jats:italic> by the sequencing of two linked novel mutations in Family 1. Most of the patients with isolated aniridia have different degrees of islet damage through related clinical tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>It is therefore noteworthy that we found different types of pathogenic mutation, which have effects of truncating or prolonging protein leaded by frameshift mutation. Our results of this study extended the pathogenic mutation spectrum of <jats:italic><jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>6<\/jats:italic> for congenital aniridia and demonstrated the male germline chimerism by molecular experiments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.481","type":"journal-article","created":{"date-parts":[[2018,10,18]],"date-time":"2018-10-18T06:11:06Z","timestamp":1539843066000},"page":"1053-1067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extension of the mutation spectrum of <i><scp>PAX<\/scp>6<\/i> from three Chinese congenital aniridia families and identification of male gonadal mosaicism"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7071-666X","authenticated-orcid":false,"given":"Zhouxian","family":"Bai","sequence":"first","affiliation":[{"name":"Genetic and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0030-7638","authenticated-orcid":false,"given":"Xiangdong","family":"Kong","sequence":"additional","affiliation":[{"name":"Genetic and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"issue":"4","key":"e_1_2_7_2_1","first-page":"802","article-title":"A double mutation in exon 6 of the beta\u2010hexosaminidase alpha subunit in a patient with the B1 variant of Tay\u2010Sachs disease","volume":"51","author":"Ainsworth P. 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