一个新PHEX基因变异导致X连锁遗传性低血磷性佝偻病的家系遗传学分析OA北大核心CSTPCD

Objective To investigate a pedigree with the clinical phenotype of hypophosphatemic rickets(HR),and the pathogenic variants was detected by whole-exome sequencing(WES)and analyzed by bioinformatics.Methods The clinical data,biochemical indicators of the HR family members were evaluated.DNA of the proband was extracted for WES experiment.PCR-Sanger sequencing and bioinformatics were performed on all members of the family to analyze the suspected pathogenic variants.The pathogenicity of mutations and their effects on protein spatial structure were predicted.Results Three generations of this family were investigated,the proband was a woman of 26 years old,and her mother and her son and daughter were diagnosed as HR by manifestations of O-shaped legs,chicken chest and low blood phosphorus level,as well as skeletal X-ray characters and high serum fibroblast growth factor 23(FGF23)level.WES identified a c.2193dupT insertion-shift heterozygous variant in PHEX(NM_000444),which resulted in a truncation of protein formation at position of 732 amino acid(p.N732*).All patients including the proband,her mother,the son and daughter carried this variant,which was classified as a likely pathogenic variant according to the new American College of Medical Genetics and Genomics(ACMG)criteria.After reviewing the literature and searching the human gene mutation database,this variant was not reported.Conclusion A novel pathogenic variant of PHEX gene is identified in this study,which provides an experimental basis for the clinical diagnosis,treatment and genetic counseling for the family.