J Korean Med Sci.  2007 Dec;22(6):981-986. 10.3346/jkms.2007.22.6.981.

PHEX Gene Mutations and Genotype-Phenotype Analysis of Korean Patients with Hypophosphatemic Rickets

• Song HR
• Park JW
• Cho DY
• Yang JH
• Yoon HR
• Jung SC

• KMID: 1785757
• DOI: http://doi.org/10.3346/jkms.2007.22.6.981

Abstract

X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH.

Keyword

Hypophosphatemic Rickets, X-linked Dominant; PHEX; Mutation; Genotype; Phenotype

MeSH Terms

Adolescent
Adult
Child
Child, Preschool
Female
Gene Dosage
Genotype
Humans
Hypophosphatemic Rickets, X-Linked Dominant/*genetics
Infant
Male
Middle Aged
*Mutation
PHEX Phosphate Regulating Neutral Endopeptidase/*genetics
Phenotype

Figure

• 

  Fig. 1 Pedigrees of patients 1 (A) and 7 (B) with X-linked hypophosphatemic rickets.

• 

  Fig. 2 Direct sequencing results demonstrate novel mutations, c.64G>T (A), c.466insAC (B), c.1174-1G>A (C), c.1699C>T (D), and c.1768+5G>A (E), in the PHEX gene in patients with X-linked hypophosphatemic rickets.

• 

  Fig. 3 Mutations of the PHEX gene identified in Korean patients with X-linked hypophosphatemic rickets. The putative transmembrane domain (TM), cysteine residues (C), and zinc-binding domains (Z) are shown below the boxes of the 22 exons. Novel mutations found in this study are shown in bold.

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