A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate
| العنوان: | A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
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| المؤلفون: | Caixia Xian, HongWen Xu, Mingwei Zhu, Weizhe Shi, YiQiang Li, Xingmei Xie, Jiangui Li, Xia Li, Jianping Wu, Ya-Ping Tang, Ping Wei, JingChun Li, Tianying Nong |
| المصدر: | Genetics and Molecular Biology Genetics and Molecular Biology v.44 n.2 2021 Sociedade Brasileira de Genética (SBG) instacron:SBG Genetics and Molecular Biology, Vol 44, Iss 2 (2021) Genetics and Molecular Biology, Volume: 44, Issue: 2, Article number: e20200334, Published: 21 MAY 2021 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0106 biological sciences, 0301 basic medicine, Osteochondroma, Hereditary multiple exostoses, QH426-470, Biology, 01 natural sciences, Frameshift mutation, 03 medical and health sciences, chemistry.chemical_compound, Exon, Skeletal disorder, Genetics, medicine, Molecular Biology, Exome sequencing, Splice site mutation, EXT2, Heparan sulfate, EXT1, medicine.disease, Stop codon, 030104 developmental biology, chemistry, Human and Medical Genetics, heparan sulfate, hereditary, 010606 plant biology & botany |
| الوصف: | Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis. |
| وصف الملف: | text/html |
| تدمد: | 1415-4757 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b97ef73660860e9d61548e9cce8634a7Test https://pubmed.ncbi.nlm.nih.gov/34042151Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b97ef73660860e9d61548e9cce8634a7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14154757 |
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