Mutational analysis and prenatal diagnosis in a family affected with hypophosphatemic rickets

Objective: To explore the clinical characteristics and genetic mutation in a family affected with hypophosphatemic rickets.

Methods: Whole exome sequencing (WES) was used to screen potential mutations in genomic DNA extracted from peripheral venous blood sample from the proband. Suspected mutation was confirmed with Sanger sequencing. Amniotic fluid was sampled from the proband for prenatal diagnosis. Potential maternal contamination was excluded by analysis of short tandem repeat (STR) markers.

Results: WES has identified a heterozygous c.2058_2059insAGTT (p.L686fs) mutation of the PHEX gene in the proband, which was confirmed by Sanger sequencing in other affected individuals from the family. The mutation was detected in the amniotic fluid sample from the fetus but not among healthy members from the family.

Conclusions: Identification of the PHEX mutation by WES has facilitated genetic counseling and prenatal diagnosis for the family affected with hypophosphatemic rickets.