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Clin Chim Acta. 2016 Sep 1;460:33-9. doi: 10.1016/j.cca.2016.06.011. Epub 2016 Jun 14.

A cryptic balanced translocation involving COL1A2 gene disruption cause a rare type of osteogenesis imperfecta.

Author information

1
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
2
Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China; Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
3
Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. Electronic address: limeilzh@sina.com.

Abstract

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.

KEYWORDS:

Balanced translocation; COL1A2; Osteogenesis imperfecta; Sequencing

PMID:
27312322
DOI:
10.1016/j.cca.2016.06.011
[Indexed for MEDLINE]

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