Chen Jing, Yang Jiangfei, Zhao Suzhou, Ying Hui, Li Guimei, Xu Chao
Department of Child Health, Xiamen Maternal and Child Health Hospital, Xiamen, Fujian, China; Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Gene. 2018 Jan 30;641:355-360. doi: 10.1016/j.gene.2017.10.062. Epub 2017 Nov 6.
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.
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.
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.
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.
软骨发育不全（HCH；OMIM 146000）是一种常见的常染色体显性骨骼发育不良，其特征为身材不成比例矮小、四肢短小、相对头大以及腰椎前凸。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，若能早期诊断，其表型可能会得到改善。
在本研究中，我们对一个患有HCH的中国家庭进行了检查，对其临床特征和影像学结果进行了归纳分析，并应用靶向外显子组测序（TES）技术进行分子诊断。
先证者及其母亲均表现为身材不成比例矮小、四肢短小粗短、L1 - L5椎弓根间距无变化、髂骨短小，坐骨切迹呈“鱼嘴状”。母亲最近因超声显示其妊娠24周时胎儿股骨长度短而接受了引产。最终，通过TES在先证者、其母亲及其胎儿中鉴定出FGFR3基因的一个新的杂合突变（c.1145G>A）；这导致第382密码子中的甘氨酸被天冬氨酸替代。
在本研究中，我们根据临床数据、影像学特征和基因检测结果诊断了一个患有HCH的中国家系。我们的结果扩展了FGFR3基因突变谱，并证明TES是临床实践中诊断骨骼发育不良的有效方法。
