Lang Steven H, Gallo Ryan A, Forghani Irman
Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Am J Med Genet A. 2022 Jun;188(6):1885-1889. doi: 10.1002/ajmg.a.62712. Epub 2022 Mar 3.
Osteogenesis imperfecta (OI) is a rare connective tissue disorder with clinical and genetic heterogeneity. The cardinal features of OI are bone fragility and low bone mineral density (BMD). Pathogenic variants in COL1A1 and COL1A2 genes, which encode the proα-1(I) and proα-2(I) chains of Type 1 collagen, are the most common causes of OI. Mutations disrupting the carboxy-terminal propeptide cleavage site of the proα-1(I) and proα-2(I) chains have recently been reported as rare causes of OI with paradoxically normal to high BMD. This report describes a father and daughter with OI who are heterozygous for a novel likely pathogenic variant at the carboxy-terminal propeptide cleavage site of COL1A1 (NM_000088.4): c.3656A>G; (p.Asp1219Gly). We describe their intrafamilial phenotypic variability and overlapping features with other COL1A1-related disorders.
成骨不全症（OI）是一种罕见的结缔组织疾病，具有临床和遗传异质性。OI的主要特征是骨骼脆弱和低骨矿物质密度（BMD）。编码I型胶原蛋白的前α-1（I）和前α-2（I）链的COL1A1和COL1A2基因中的致病变异是OI最常见的原因。最近有报道称，破坏前α-1（I）和前α-2（I）链羧基末端前肽切割位点的突变是OI的罕见原因，其骨密度反常地正常至高。本报告描述了一对患有OI的父女，他们在COL1A1（NM_000088.4）的羧基末端前肽切割位点存在一种新的可能致病变异的杂合子：c.3656A>G；（p.Asp1219Gly）。我们描述了他们家族内的表型变异性以及与其他COL1A1相关疾病的重叠特征。
