Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia
Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia
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中国软骨发育不全家系 FGFR3 基因新突变的鉴定
DOI：
10.1016/j.gene.2017.10.062
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发表时间：
2018-01-30
期刊：
影响因子：
3.5
通讯作者：
Xu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Jing;Yang, Jiangfei;Xu, Chao
背景：软骨发育不良（HCH; OMIM 146000）是一种常见的常染色体显性骨骼发育不良，其特征是不成比例的身材矮小、四肢短、相对大头畸形和腰椎前凸。由于其临床和遗传异质性，基因突变分析在诊断中尤为重要，如果早期诊断可能会改善表型。材料和方法：在本研究中，我们检查了一个中国HCH家庭，对其临床特征和影像学结果进行归纳分析，并应用靶向外显子组测序（TES）技术进行分子诊断。结果：先证者及其母亲均呈不成比例的矮小身材，四肢短而粗短，L1 - L5椎间距离不变，髂骨短，有“鱼嘴型”坐骨切迹。这位母亲最近接受了人工流产手术，因为超声检查显示她怀孕24周的胎儿股骨长度短。最终，在先证者、他的母亲和她的胎儿中，通过TES鉴定出了FGFR3中一个新的杂合突变（c.1145G > a）；这导致密码子382中的甘氨酸被天冬氨酸取代。结论：在本研究中，我们根据临床资料、放射学特征和基因检测结果诊断了一个中国家系HCH。我们的研究结果扩展了FGFR3的基因突变谱，并证明TES在临床实践中是诊断骨骼发育不良的有效方法。
Background: Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early.Materials and methods: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis.Results: The proband and his mother all presented disproportionate short stature, short, stubby extremities, unchanged interpedicular distances from L1 - L5, and short iliac bones, with a 'fish mouth -shaped' sciatic notch. The mother received induced abortion recently because an ultrasound showed short femur length of her fetus at 24-week gestation. Eventually, a novel heterozygous mutation (c.1145G > A) in FGFR3 was identified by TES in the proband, his mother, and her fetus; this causes the substitution of glycine with aspartic acid in codon 382.Conclusions: In this study, we diagnosed a Chinese pedigree with HCH based on clinical data, radiographic features, and genetic testing results. Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.