دورية أكاديمية
Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism.
| العنوان: | Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism. |
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| المؤلفون: | Bai Z; Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Kong X; Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. |
| المصدر: | Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2018 Nov; Vol. 6 (6), pp. 1053-1067. Date of Electronic Publication: 2018 Oct 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101603758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2324-9269 (Electronic) Linking ISSN: 23249269 NLM ISO Abbreviation: Mol Genet Genomic Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Hoboken, NJ] : John Wiley & Sons, [2013]- |
| مواضيع طبية MeSH: | Mosaicism* , Mutation*, Aniridia/*genetics , Gonads/*metabolism , PAX6 Transcription Factor/*genetics, Adolescent ; Adult ; Aniridia/pathology ; Child, Preschool ; Female ; Gonads/pathology ; Humans ; Islets of Langerhans/pathology ; Male ; Middle Aged ; Pedigree |
| مستخلص: | Background: Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. PAX6 is the main disease-causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder. Methods: 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 PCR-based 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. Results: We identified four novel mutations of PAX6 from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880delCA (p.S294Cfs*46) and c.1124C>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 PAX6 are co-segregated with the aniridia from controls in the families, but the novel missense mutation is not co-segregated 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 PAX6 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. Conclusion: 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 PAX6 for congenital aniridia and demonstrated the male germline chimerism by molecular experiments. (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.) |
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| فهرسة مساهمة: | Keywords: PAX6; congenital aniridia; double mutation; frameshift mutation; male gonadal mosaicism |
| المشرفين على المادة: | 0 (PAX6 Transcription Factor) 0 (PAX6 protein, human) |
| تواريخ الأحداث: | Date Created: 20181019 Date Completed: 20190123 Latest Revision: 20210109 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6305634 |
| DOI: | 10.1002/mgg3.481 |
| PMID: | 30334364 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2324-9269 |
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| DOI: | 10.1002/mgg3.481 |