Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing
Abstract The protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene is one of 18 genes involved in the pathogenesis of α-dystroglycanopathies(α-DGPs) such as muscle–eye–brain disease (MEB). Our study aimed to retrospectively analyze and characterize the clinical and genetic feat...
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oai:doaj.org-article:bdc70500ec3244ecb6dfec4e93dc57652021-12-02T15:05:48ZNovel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing10.1038/s41598-017-07349-82045-2322https://doaj.org/article/bdc70500ec3244ecb6dfec4e93dc57652017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07349-8https://doaj.org/toc/2045-2322Abstract The protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene is one of 18 genes involved in the pathogenesis of α-dystroglycanopathies(α-DGPs) such as muscle–eye–brain disease (MEB). Our study aimed to retrospectively analyze and characterize the clinical and genetic features of three MEB patients with POMGNT1 mutations. One female and two male patients from three unrelated families were diagnosed with MEB, manifesting hypotonia at birth, mental retardation, structural brain defects, and ocular malformations. The novel missense mutations c.296 T > C and c.794 G > C were revealed in patient 2 and patient 3 respectively by next-generation sequencing (NGS). Further NGS data analysis revealed that all three patients had the same novel copy number variations (CNV) g.6668-8257del, which was homozygous in patient 1 and heterozygous in patients 2 and 3. By long-range polymerase chain reaction (PCR) and Sanger sequencing, it was shown that the two breakpoints of the CNV localized to two AluY elements and displayed 42-bp of microhomology. The CNV was confirmed as a founder mutation by haplotype analysis. Our study indicated that NGS is a clinically useful method of detecting α-DGPs genes -related CNV, and the CNV is likely to be caused by Alu-Alu recombination or from a single ancestor bearing the deletion chromosome.Xiaona FuHaipo YangHui JiaoShuo WangAijie LiuXiaoqing LiJiangxi XiaoYanling YangXiru WuHui XiongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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Medicine R Science Q Xiaona Fu Haipo Yang Hui Jiao Shuo Wang Aijie Liu Xiaoqing Li Jiangxi Xiao Yanling Yang Xiru Wu Hui Xiong Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| description |
Abstract The protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene is one of 18 genes involved in the pathogenesis of α-dystroglycanopathies(α-DGPs) such as muscle–eye–brain disease (MEB). Our study aimed to retrospectively analyze and characterize the clinical and genetic features of three MEB patients with POMGNT1 mutations. One female and two male patients from three unrelated families were diagnosed with MEB, manifesting hypotonia at birth, mental retardation, structural brain defects, and ocular malformations. The novel missense mutations c.296 T > C and c.794 G > C were revealed in patient 2 and patient 3 respectively by next-generation sequencing (NGS). Further NGS data analysis revealed that all three patients had the same novel copy number variations (CNV) g.6668-8257del, which was homozygous in patient 1 and heterozygous in patients 2 and 3. By long-range polymerase chain reaction (PCR) and Sanger sequencing, it was shown that the two breakpoints of the CNV localized to two AluY elements and displayed 42-bp of microhomology. The CNV was confirmed as a founder mutation by haplotype analysis. Our study indicated that NGS is a clinically useful method of detecting α-DGPs genes -related CNV, and the CNV is likely to be caused by Alu-Alu recombination or from a single ancestor bearing the deletion chromosome. |
| format |
article |
| author |
Xiaona Fu Haipo Yang Hui Jiao Shuo Wang Aijie Liu Xiaoqing Li Jiangxi Xiao Yanling Yang Xiru Wu Hui Xiong |
| author_facet |
Xiaona Fu Haipo Yang Hui Jiao Shuo Wang Aijie Liu Xiaoqing Li Jiangxi Xiao Yanling Yang Xiru Wu Hui Xiong |
| author_sort |
Xiaona Fu |
| title |
Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| title_short |
Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| title_full |
Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| title_fullStr |
Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| title_full_unstemmed |
Novel copy number variation of POMGNT1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| title_sort |
novel copy number variation of pomgnt1 associated with muscle-eye-brain disease detected by next-generation sequencing |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/bdc70500ec3244ecb6dfec4e93dc5765 |
| work_keys_str_mv |
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