CONTEXT: Familial hypophosphatemic rickets is usually transmitted as an X-linked 
dominant disorder (XLH), although autosomal dominant forms have also been 
observed. Genetic studies of these disorders have identified mutations in PHEX 
and FGF23 as the causes of X-linked dominant disorder and autosomal dominant 
forms, respectively.
OBJECTIVE: The objective of the study was to describe the molecular genetic 
findings in a family affected by hypophosphatemic rickets with presumed 
autosomal dominant inheritance.
PATIENTS: We studied a family in which the father and the elder of his two 
daughters, but not the second daughter, were affected by hypophosphatemic 
rickets. The pedigree interpretation of the family suggested that genetic 
transmission of the disorder occurred as an autosomal dominant trait.
METHODS AND RESULTS: Direct nucleotide sequencing of FGF23 and PHEX revealed 
that the elder daughter was heterozygous for an R567X mutation in PHEX, rather 
than FGF23, suggesting that the genetic transmission occurred as an X-linked 
dominant trait. Unexpectedly, the father was heterozygous for this mutation. 
Single-nucleotide primer extension and denaturing HPLC analysis of the father 
using DNA from single hair roots revealed that he was a somatic mosaic for the 
mutation. Haplotype analysis confirmed that the father transmitted the genotypes 
for 18 markers on the X chromosome equally to his two daughters. The fact that 
the father transmitted the mutation to only one of his two daughters indicated 
that he was a germline mosaic for the mutation.
CONCLUSIONS: Somatic and germline mosaicism for an X-linked dominant mutation in 
PHEX may mimic autosomal dominant inheritance.