Identification of a novel mutation in the FGFR3 gene in a Chinese family with Hypochondroplasia

Abstract 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.