title: Novel de novo nonsense mutation of the PHEX gene (p.Lys50Ter) in a Chinese patient with hypophosphatemic rickets.
abstract: X-linked hypophosphatemic rickets (XLHR), the most common form of inherited rickets, is a dominant disorder characterized by hypophosphatemia, abnormal bone mineralization, and short stature. Mutations in the PHEX gene are major causes of XLHR. Herein, we clinically characterized four unrelated families with hypophosphatemia, bone abnormalities, short stature, and dentin malformation. Mutational analysis of the PHEX gene using Sanger sequencing revealed three recurrent mutations (c.2197T>C, c.1646G>C, and c.2198G>A) and a de novo nonsense mutation (c.148A>T). The novel mutation was not found in any of the unaffected family members or in the 100 healthy controls and was predicted to produce a truncated protein (p.K50X), a truncated form of the PHEX protein caused by nonsense mutations has been frequently detected in XLHR individuals. Thus, our work indicated that the c.148A>T (p.K50X) mutation was the likely pathogenic mutation in individual III-2 in family 2, and that PHEX gene mutations were responsible for XLHR in these Chinese families. These findings expand the mutation spectrum of PHEX and may help us to understand the molecular basis of XLHR in order to facilitate genetic counseling.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Libin
authors.initials: L
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Baoheng
authors.initials: B
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Jiazhen
authors.initials: J
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Pu
authors.initials: P
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, PR China. Electronic address: wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Wu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D018389:Codon, Nonsense; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human
keywords: Nonsense mutation; PHEX; Truncated protein; X-linked hypophosphatemic rickets