McInerney-Leo A M, Duncan E L, Leo P J, Gardiner B, Bradbury L A, Harris J E, Clark G R, Brown M A, Zankl A
Human Genetics Group, The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia.
Department of Endocrinology, Royal Brisbane and Women's Hospital, Herston, QLD, 4029, Australia.
Clin Genet. 2015 Jul;88(1):49-55. doi: 10.1111/cge.12440. Epub 2014 Aug 15.
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.
颌骨干骺端发育异常（GDD）是一种罕见的常染色体显性疾病，其特征为骨质脆弱、骨矿物质密度（BMD）不规则以及颅骨和颌骨的纤维性骨病变。在某些病例中已鉴定出 anoctamin - 5（ANO5）基因突变。我们旨在通过全外显子捕获和大规模平行测序（WES），在一个具有GDD特征但ANO5无突变的家族中鉴定致病突变。对两名受影响个体（一位母亲和儿子）以及母亲未受影响的父母进行WES，在COL1A1的C - 前肽裂解位点发现了一个突变。在成骨不全（OI）个体中也曾报道过类似突变，且骨密度异常升高。COL1A1的C - 前肽裂解位点突变不仅可能导致“高骨量OI”，还可能导致GDD的临床特征，特别是颅骨和颌骨中不规则的硬化性骨密度和纤维性骨病变。对于ANO5突变阴性的GDD患者，应评估其I型胶原C - 前肽裂解位点的突变情况。
