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Familial hypophosphatemic rickets caused by a large deletion in PHEX gene.
Eur J Endocrinol. 2009 Oct; 161(4):647-51.EJ

Abstract

CONTEXT

X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR) share common clinical features including high fibroblast growth factor 23 (FGF23) levels. These diseases are caused by mutations in phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and dentin matrix acidic phosphoprotein 1 (DMP1) gene respectively. It remains unclear whether these diseases can be clinically discriminated.

OBJECTIVE

To clarify the underlying mechanism of patients with hypophosphatemic rickets whose parents showed no physical findings suggesting rickets.

DESIGN AND PATIENTS

The proband is a 39-year-old woman. She and her 37-year-old brother show the same clinical features such as bowing of legs together with hypophosphatemia (sister: P 1.8 mg/dl, brother: P 1.6 mg/dl) and high FGF23 levels (sister: 542 pg/ml, brother: 96 pg/ml). Physical findings of their parents are normal and ARHR was suspected.

RESULTS

Sequencing of all coding exons and exon-intron junctions of DMP1 and FGF23 genes showed no mutation. Subsequent analysis revealed that there is a deletion of 52 143 bp including exons 1-3 in PHEX gene in the brother. His sister was found to be a heterozygote for the same deletion indicating that they are suffering from XLH. The same deletion was detected in the mother. However, the amount of the wild-type allele was more and that of the mutant one was less in genomic DNA from the mother compared with those from the sister. Single nucleotide polymorphism (SNP) analysis indicated that the mother has three kinds of PHEX alleles suggesting a somatic mosaicism.

CONCLUSION

Careful genetic analysis is mandatory for correct differential diagnosis of hypophosphatemic rickets with high FGF23 levels.

Authors+Show Affiliations

Division of Pediatrics, Department of Medicine, University of Tokyo Hospital, Tokyo 113-8655, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19581284

Citation

Saito, Tasuku, et al. "Familial Hypophosphatemic Rickets Caused By a Large Deletion in PHEX Gene." European Journal of Endocrinology, vol. 161, no. 4, 2009, pp. 647-51.
Saito T, Nishii Y, Yasuda T, et al. Familial hypophosphatemic rickets caused by a large deletion in PHEX gene. Eur J Endocrinol. 2009;161(4):647-51.
Saito, T., Nishii, Y., Yasuda, T., Ito, N., Suzuki, H., Igarashi, T., Fukumoto, S., & Fujita, T. (2009). Familial hypophosphatemic rickets caused by a large deletion in PHEX gene. European Journal of Endocrinology, 161(4), 647-51. https://doi.org/10.1530/EJE-09-0261
Saito T, et al. Familial Hypophosphatemic Rickets Caused By a Large Deletion in PHEX Gene. Eur J Endocrinol. 2009;161(4):647-51. PubMed PMID: 19581284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Familial hypophosphatemic rickets caused by a large deletion in PHEX gene. AU - Saito,Tasuku, AU - Nishii,Yutaka, AU - Yasuda,Toshiyuki, AU - Ito,Nobuaki, AU - Suzuki,Hisanori, AU - Igarashi,Takashi, AU - Fukumoto,Seiji, AU - Fujita,Toshiro, Y1 - 2009/07/06/ PY - 2009/7/8/entrez PY - 2009/7/8/pubmed PY - 2009/10/6/medline SP - 647 EP - 51 JF - European journal of endocrinology JO - Eur J Endocrinol VL - 161 IS - 4 N2 - CONTEXT: X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant and recessive hypophosphatemic rickets/osteomalacia (ADHR and ARHR) share common clinical features including high fibroblast growth factor 23 (FGF23) levels. These diseases are caused by mutations in phosphate regulating endopeptidase homolog, X-linked (PHEX), FGF23, and dentin matrix acidic phosphoprotein 1 (DMP1) gene respectively. It remains unclear whether these diseases can be clinically discriminated. OBJECTIVE: To clarify the underlying mechanism of patients with hypophosphatemic rickets whose parents showed no physical findings suggesting rickets. DESIGN AND PATIENTS: The proband is a 39-year-old woman. She and her 37-year-old brother show the same clinical features such as bowing of legs together with hypophosphatemia (sister: P 1.8 mg/dl, brother: P 1.6 mg/dl) and high FGF23 levels (sister: 542 pg/ml, brother: 96 pg/ml). Physical findings of their parents are normal and ARHR was suspected. RESULTS: Sequencing of all coding exons and exon-intron junctions of DMP1 and FGF23 genes showed no mutation. Subsequent analysis revealed that there is a deletion of 52 143 bp including exons 1-3 in PHEX gene in the brother. His sister was found to be a heterozygote for the same deletion indicating that they are suffering from XLH. The same deletion was detected in the mother. However, the amount of the wild-type allele was more and that of the mutant one was less in genomic DNA from the mother compared with those from the sister. Single nucleotide polymorphism (SNP) analysis indicated that the mother has three kinds of PHEX alleles suggesting a somatic mosaicism. CONCLUSION: Careful genetic analysis is mandatory for correct differential diagnosis of hypophosphatemic rickets with high FGF23 levels. SN - 1479-683X UR - https://www.unboundmedicine.com/medline/citation/19581284/Familial_hypophosphatemic_rickets_caused_by_a_large_deletion_in_PHEX_gene_ L2 - https://eje.bioscientifica.com/doi/10.1530/EJE-09-0261 DB - PRIME DP - Unbound Medicine ER -