A cryptic balanced translocation involving COL1A2 gene disruption cause a rare type of osteogenesis imperfecta
| Autor: | Yu-wen Song, Ou Wang, Weibo Xia, Xiao-jie Xu, Fang Lv, Li-jie Song, Yi Liu, Yan Jiang, Asan, Jian-yi Wang, Xiaoping Xing, Jiawei Wang, Mei Li |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Chromosomal translocation Biology Biochemistry PPP2R2B Collagen Type I Translocation Genetic 03 medical and health sciences Exon symbols.namesake Chromosome Breakpoints 0302 clinical medicine medicine Humans Sanger sequencing Chromosome 7 (human) Genetics Biochemistry (medical) Breakpoint General Medicine Osteogenesis Imperfecta medicine.disease Pedigree 030104 developmental biology Osteogenesis imperfecta Child Preschool symbols Chromosomes Human Pair 5 030217 neurology & neurosurgery Type I collagen Chromosomes Human Pair 7 |
| Zdroj: | Clinica chimica acta; international journal of clinical chemistry. 460 |
| ISSN: | 1873-3492 |
| Popis: | Background Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by low bone mass and recurrent fractures. Most OI cases follow an autosomal dominant pattern of inheritance and are attributed to mutations in genes encoding type I collagen ( COL1A1 / COL1A2 ). Genomic structural variations involving type I collagen genes are extremely rare in OI. Case report In this study, we characterized a de novo balanced translocation of t(5;7)(q32;q21.3) that caused an extremely rare type of OI in a patient from a non-consanguineous family. The clinical phenotypes of this OI included recurrent fractures, low bone mass, macrocephaly, blue sclera and failure to thrive. Next-generation sequencing was used to identify the translocation, and Sanger sequencing was used to validate and map the breakpoints. The breakpoint on chromosome 7 disrupted the COL1A2 gene in the 17th exon, presumed to affect type I collagen production and give rise to OI. The breakpoint on chromosome 5 disrupted the protein phosphatase 2 regulatory subunit B, beta gene ( PPP2R2B ) within the first intron. Conclusions This is the first report of a copy-neutral structural variant involving COL1A2 that leads to a rare type of OI. This study expands the genotypic spectrum of OI and demonstrates the effectiveness of targeted sequencing for breakpoint mapping. |
| Databáze: | OpenAIRE |
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