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Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens.
Exp Clin Endocrinol Diabetes. 2011 Jul; 119(7):431-5.EC

Abstract

INTRODUCTION

The most common form of familial hypophosphatemic rickets is X-linked. PHEX has been identified as the gene defective in this phosphate wasting disorder leading to decreased renal phosphate reabsorption, hypophosphatemia and inappropriate concentrations of 1,25-dihydroxyvitamin D in regard to hypophosphatemia. Clinical manifestation are skeletal deformities, short stature, osteomalacia, dental abscesses, bone pain, and loss of hearing.

SUBJECTS AND METHODS

We report 3 cases of hypophosphatemic rickets with genetic mutational analysis of the PHEX gene. In 1 male patient an unknown nonsense mutation was found in exon 7, codon 245 (c.735T>G, Tyr245Term, Y245X). In both female patients known mutations were found: c.682delTC (exon 6, codon 228) and c.1952G>C (exon 19, codon 651, R651P). Age at diagnosis ranged from early childhood to the age of 35 years. Clinical complications were hip replacement in 1 patient, mild nephrocalcinosis in 2 patients and loss of hearing in 1 patient. All 3 patients have been treated with phosphate supplements and receive 1,25-dihydroxyvitamin D. Under this regimen all patients show stable biochemical markers with slight hyperparathyreoidism. In all patients at least one family member is affected by rickets, as well.

CONCLUSIONS

We report a novel nonsense mutation of PHEX that has not been identified so far. The recent discovery of FGF23 and MEPE has changed our understanding of the kidney-bone metabolism, but also raises concerns about the efficacy of current therapeutic regimens that are reviewed in this context.

Authors+Show Affiliations

Department of Clinical Endocrinology, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Review

Language

eng

PubMed ID

21553362

Citation

Kienitz, T, et al. "Novel PHEX Nonsense Mutation in a Patient With X-linked Hypophosphatemic Rickets and Review of Current Therapeutic Regimens." Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, vol. 119, no. 7, 2011, pp. 431-5.
Kienitz T, Ventz M, Kaminsky E, et al. Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens. Exp Clin Endocrinol Diabetes. 2011;119(7):431-5.
Kienitz, T., Ventz, M., Kaminsky, E., & Quinkler, M. (2011). Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, 119(7), 431-5. https://doi.org/10.1055/s-0031-1277162
Kienitz T, et al. Novel PHEX Nonsense Mutation in a Patient With X-linked Hypophosphatemic Rickets and Review of Current Therapeutic Regimens. Exp Clin Endocrinol Diabetes. 2011;119(7):431-5. PubMed PMID: 21553362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel PHEX nonsense mutation in a patient with X-linked hypophosphatemic rickets and review of current therapeutic regimens. AU - Kienitz,T, AU - Ventz,M, AU - Kaminsky,E, AU - Quinkler,M, Y1 - 2011/05/06/ PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/11/10/medline SP - 431 EP - 5 JF - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JO - Exp Clin Endocrinol Diabetes VL - 119 IS - 7 N2 - INTRODUCTION: The most common form of familial hypophosphatemic rickets is X-linked. PHEX has been identified as the gene defective in this phosphate wasting disorder leading to decreased renal phosphate reabsorption, hypophosphatemia and inappropriate concentrations of 1,25-dihydroxyvitamin D in regard to hypophosphatemia. Clinical manifestation are skeletal deformities, short stature, osteomalacia, dental abscesses, bone pain, and loss of hearing. SUBJECTS AND METHODS: We report 3 cases of hypophosphatemic rickets with genetic mutational analysis of the PHEX gene. In 1 male patient an unknown nonsense mutation was found in exon 7, codon 245 (c.735T>G, Tyr245Term, Y245X). In both female patients known mutations were found: c.682delTC (exon 6, codon 228) and c.1952G>C (exon 19, codon 651, R651P). Age at diagnosis ranged from early childhood to the age of 35 years. Clinical complications were hip replacement in 1 patient, mild nephrocalcinosis in 2 patients and loss of hearing in 1 patient. All 3 patients have been treated with phosphate supplements and receive 1,25-dihydroxyvitamin D. Under this regimen all patients show stable biochemical markers with slight hyperparathyreoidism. In all patients at least one family member is affected by rickets, as well. CONCLUSIONS: We report a novel nonsense mutation of PHEX that has not been identified so far. The recent discovery of FGF23 and MEPE has changed our understanding of the kidney-bone metabolism, but also raises concerns about the efficacy of current therapeutic regimens that are reviewed in this context. SN - 1439-3646 UR - https://www.unboundmedicine.com/medline/citation/21553362/Novel_PHEX_nonsense_mutation_in_a_patient_with_X_linked_hypophosphatemic_rickets_and_review_of_current_therapeutic_regimens_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0031-1277162 DB - PRIME DP - Unbound Medicine ER -