title: Prenatal diagnosis for a novel splice mutation of PHEX gene in a large Han Chinese family affected with X-linked hypophosphatemic rickets.
abstract: BACKGROUND
  X-linked hypophosphatemia (XLH) is the most common form of heritable rickets characterized by X-linked dominant inheritance, renal phosphate wasting, hypophosphatemia, and defective bone mineralization. Inactivating mutations of the PHEX gene located at Xp22.1 have been linked with this disease. Ethnic distribution of such mutations seems widespread but only a few mutations in the Chinese population have been reported to date.
  
  
  METHODS
  We report on a large Han Chinese family affected with XLH rickets, which included 13 patients from four generations. Polymerase chain reaction and direct sequencing were performed for all exons and intron-exon boundaries of the PHEX gene. The effect of nucleotide changes was analyzed using bioinformatic software. Prenatal diagnosis was performed on umbilical cord blood at the 20th gestational week.
  
  
  RESULTS
  A novel G-->A splice mutation in intron 7 (c.849+1G>A) was identified in all patients from the family. As confirmed by reverse-transcription (RT)-polymerase chain reaction (PCR), the mutation has rendered loss of a normal splice donor site (c.849+1G) while activating a cryptic one at c.849+519G, which resulted in addition of 518 nucleotides to the mature RNA. Prenatal diagnosis had excluded the fetus for carrying the same mutation. A healthy boy was born later.
  
  
  CONCLUSIONS
  A novel splice mutation c.849+1G>A in the PHEX gene is responsible for XLH in the studied family. Further studies may enhance our understanding of the role of this mutation in the pathogenesis of XLH.
authors.affiliation: Department of Medical Genetics, School of Basic Medicine, China Medical University, Shenyang, China.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Qiu
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhou
authors.forename: Peiyan
authors.initials: P
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Hongkun
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Hou
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kailai
authors.initials: K
authors.lastname: Sun
authors.forename: Jesse
authors.initials: J
authors.lastname: Li-Ling
mesh_terms: D017398:Alternative Splicing; D002681:China / Q000208:ethnology; D019295:Computational Biology; D005091:Exons / Q000235:genetics; D053098:Familial Hypophosphatemic Rickets / Q000175:diagnosis* / Q000235:genetics; D005190:Family; D005260:Female; D040181:Genetic Diseases, X-Linked; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA
chemical_list: D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human