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

Affiliations
  • 1Department of Orthopedic Surgery, Rare Diseases Institute, Korea University Guro Hospital, Seoul, Korea.
  • 2Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Korea. jungsc@ewha.ac.kr
  • 3Clinical Research Institute, Labgenomics Co., Ltd., Seoul, Korea.
  • 4Department of Biomedical and Analytical Chemistry, College of Pharmacy, Duksung Women s University, Seoul, Korea.

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.


Cited by  3 articles

A novel de novo mutation within PHEX gene in a young girl with hypophosphatemic rickets and review of literature
Chong Kun Cheon, Hoon Sang Lee, Su Yung Kim, Min Jung Kwak, Gu-Hwan Kim, Han-Wook Yoo
Ann Pediatr Endocrinol Metab. 2014;19(1):36-41.    doi: 10.6065/apem.2014.19.1.36.

A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets
Misun Yang, Jinsup Kim, Aram Yang, Jahyun Jang, Tae Yeon Jeon, Sung Yoon Cho, Dong-Kyu Jin
Ann Pediatr Endocrinol Metab. 2018;23(4):229-234.    doi: 10.6065/apem.2018.23.4.229.

Identification of a novel variant in the PHEX gene using targeted gene panel sequencing in a 24-month-old boy with hypophosphatemic rickets
Ha Young Jo, Jung Hyun Shin, Hye Young Kim, Young Mi Kim, Heirim Lee, Mi Hye Bae, Kyung Hee Park, Ja-Hyun Jang, Min Jung Kwak
Ann Pediatr Endocrinol Metab. 2020;25(1):63-67.    doi: 10.6065/apem.2020.25.1.63.


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