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COL1A1 C‐propeptide cleavage site mutation causes high bone mass, bone fragility and jaw lesions: a new cause of gnathodiaphyseal dysplasia?
Author(s) -
McInerneyLeo A. M.,
Duncan E. L.,
Leo P. J.,
Gardiner B.,
Bradbury L. A.,
Harris J. E.,
Clark G. R.,
Brown M. A.,
Zankl A.
Publication year - 2015
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12440
Subject(s) - bone mass , mutation , cleavage (geology) , fragility , dysplasia , medicine , genetics , biology , chemistry , osteoporosis , gene , paleontology , fracture (geology)
Gnathodiaphyseal dysplasia ( GDD ) is a rare autosomal dominant condition characterized by bone fragility, irregular bone mineral density ( BMD ) and fibro‐osseous lesions in the skull and jaw. Mutations in Anoctamin‐5 ( ANO5 ) have been identified in some cases. We aimed to identify the causative mutation in a family with features of GDD but no mutation in ANO5 , using whole exome capture and massive parallel sequencing ( WES ). WES of two affected individuals (a mother and son) and the mother's unaffected parents identified a mutation in the C‐propeptide cleavage site of COL1A1 . Similar mutations have been reported in individuals with osteogenesis imperfecta (OI) and paradoxically increased BMD. C‐propeptide cleavage site mutations in COL1A1 may not only cause ‘high bone mass OI ’, but also the clinical features of GDD , specifically irregular sclerotic BMD and fibro‐osseous lesions in the skull and jaw. GDD patients negative for ANO5 mutations should be assessed for mutations in type I collagen C‐propeptide cleavage sites.