Rare Diseases Symptoms Automatic Extraction

A novel missense mutation of FGFR3 in a Chinese female and her fetus with Hypochondroplasia by next-generation sequencing.


Hypochondroplasia (HCH) is a mild, autosomal dominant human skeletal dysplasias characterized by short extremities, short stature and lumbar lordosis. There are three other kinds of dwarfism (Pseudoachondroplasia, Achondroplasia and Thanatophoric Syndromes) with similar clinical features, which makes it difficult to give a precise diagnosis. Molecular genetic analysis of related genes should be employed.In this study, we reported a Chinese family diagnosed as a type of skeletal dysplasia based on clinical and radiologic findings. To make an accurate diagnosis quickly and economically, we performed microarray-based next-generation sequencing (NGS) to detect the variants in the disease-related genes (FGFR3 and COMP).The mother presents short limbed stature, short iliac bones, short femoral necks, short stubby tibia and mildly increased fibular length and genu varum. Her fetus demonstrated abnormally short femur at 23 and 28week's gestation by ultrasound scan, and was highly suspected with dwarfism. Eventually, a novel missense mutation (c.1024G>T) in FGFR3 was identified by next-generation sequencing. The substitution is found in both the mother and her fetus. The mutation was further confirmed by Sanger sequencing.This is the first report of missense mutation identified in the IgIII domain of the FGFR3 gene using NGS. Our results extended the mutational spectrum of FGFR3 and proved that applications of NGS and bioinformatics are effective methods for skeletal dysplasia diagnosis in clinical practices.