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.
MATERIALS AND 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.