Abstract：
Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene.
Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein.
The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.
Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein.
The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.
摘要：
短指B型是一种常染色体显性疾病，其特征是远端指骨和指甲发育不全，可分为短指B1型（BDB1）和短指B2型（BDB2）。BDB1是短指的最严重形式，是由受体酪氨酸激酶样孤儿受体2（ROR2）基因中的截短变体引起的。
这里,我们报告了一个五代中国家庭，有或没有并肢。先证者和她的母亲同时经历了数字分离，并提供了先证者和她父母的基因分析。新的杂合移码变体c.1320dupG，通过全外显子组测序和Sanger测序在受影响的个体中鉴定出ROR2基因中的p.(Arg441Alafs*18)。预测ROR2中的c.1320dupG变体会产生截短的蛋白质，该蛋白质缺乏酪氨酸激酶和富含丝氨酸/苏氨酸和脯氨酸的结构，并显着改变了突变ROR2蛋白质的三级结构。
c.1320dupG,迄今为止，ROR2基因中的p.（Arg441Alafs*18）变体尚未在任何数据库中报道，因此是新颖的。我们的研究扩展了短指的基因变异谱，可能为家庭成员的遗传咨询提供信息。
这里,我们报告了一个五代中国家庭，有或没有并肢。先证者和她的母亲同时经历了数字分离，并提供了先证者和她父母的基因分析。新的杂合移码变体c.1320dupG，通过全外显子组测序和Sanger测序在受影响的个体中鉴定出ROR2基因中的p.(Arg441Alafs*18)。预测ROR2中的c.1320dupG变体会产生截短的蛋白质，该蛋白质缺乏酪氨酸激酶和富含丝氨酸/苏氨酸和脯氨酸的结构，并显着改变了突变ROR2蛋白质的三级结构。
c.1320dupG,迄今为止，ROR2基因中的p.（Arg441Alafs*18）变体尚未在任何数据库中报道，因此是新颖的。我们的研究扩展了短指的基因变异谱，可能为家庭成员的遗传咨询提供信息。
