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Novel and de novo PHEX mutations in patients with hypophosphatemic rickets.
Bone. 2013 Jan; 52(1):286-91.BONE

Abstract

X-linked hypophosphatemic rickets (XLH) is the most common inherited rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in 10 patients from 6 unrelated Turkish families by PCR-sequence analysis. Six different PHEX mutations were detected in the patients. Four of them were novel: c.1217G>A (p.C406Y) in exon 11, c.2078G>T (p.C693F) in exon 21, a splice donor site mutation in intron 13 (IVS13+1G>T), and a splice acceptor site mutation in intron 13 (IVS13-2A>G). De novo PHEX mutations were found exclusively in female patients from 4 families and inherited mutations were detected from remaining two families. The patients' phenotype was consistent with the loss of PHEX function. Literature review of 78 sporadic cases shows that de novo mutations are present in 83% female patients and female/male ratio is 5 to 1. One patient had biallilic PHEX mutations at c.1735G>A (p.G579R) whereas her mother and two siblings carried a monoallelic mutation. The clinical and laboratory findings of the patient with biallilic PHEX mutation were similar to those with monoallelic mutation. The study shows that PHEX mutation is a common cause of either familial or sporadic hypophosphatemic rickets in Turkish population. Gene dosage effect is not observed. The frequent de novo mutations found in the female patients are likely resulting from mutagenesis of X chromosome in paternal germ cells.

Authors+Show Affiliations

Department of Pediatric Endocrinology, Akdeniz University School of Medicine, Antalya, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23079138

Citation

Durmaz, Erdem, et al. "Novel and De Novo PHEX Mutations in Patients With Hypophosphatemic Rickets." Bone, vol. 52, no. 1, 2013, pp. 286-91.
Durmaz E, Zou M, Al-Rijjal RA, et al. Novel and de novo PHEX mutations in patients with hypophosphatemic rickets. Bone. 2013;52(1):286-91.
Durmaz, E., Zou, M., Al-Rijjal, R. A., Baitei, E. Y., Hammami, S., Bircan, I., Akçurin, S., Meyer, B., & Shi, Y. (2013). Novel and de novo PHEX mutations in patients with hypophosphatemic rickets. Bone, 52(1), 286-91. https://doi.org/10.1016/j.bone.2012.10.012
Durmaz E, et al. Novel and De Novo PHEX Mutations in Patients With Hypophosphatemic Rickets. Bone. 2013;52(1):286-91. PubMed PMID: 23079138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel and de novo PHEX mutations in patients with hypophosphatemic rickets. AU - Durmaz,Erdem, AU - Zou,Minjing, AU - Al-Rijjal,Roua A, AU - Baitei,Essa Y, AU - Hammami,Sumaya, AU - Bircan,Iffet, AU - Akçurin,Sema, AU - Meyer,Brian, AU - Shi,Yufei, Y1 - 2012/10/16/ PY - 2012/08/27/received PY - 2012/10/07/revised PY - 2012/10/08/accepted PY - 2012/10/20/entrez PY - 2012/10/20/pubmed PY - 2013/3/26/medline SP - 286 EP - 91 JF - Bone JO - Bone VL - 52 IS - 1 N2 - X-linked hypophosphatemic rickets (XLH) is the most common inherited rickets. XLH is caused by inactivating mutations in the PHEX gene and is transmitted as an X-linked dominant disorder. We investigated PHEX mutation in 10 patients from 6 unrelated Turkish families by PCR-sequence analysis. Six different PHEX mutations were detected in the patients. Four of them were novel: c.1217G>A (p.C406Y) in exon 11, c.2078G>T (p.C693F) in exon 21, a splice donor site mutation in intron 13 (IVS13+1G>T), and a splice acceptor site mutation in intron 13 (IVS13-2A>G). De novo PHEX mutations were found exclusively in female patients from 4 families and inherited mutations were detected from remaining two families. The patients' phenotype was consistent with the loss of PHEX function. Literature review of 78 sporadic cases shows that de novo mutations are present in 83% female patients and female/male ratio is 5 to 1. One patient had biallilic PHEX mutations at c.1735G>A (p.G579R) whereas her mother and two siblings carried a monoallelic mutation. The clinical and laboratory findings of the patient with biallilic PHEX mutation were similar to those with monoallelic mutation. The study shows that PHEX mutation is a common cause of either familial or sporadic hypophosphatemic rickets in Turkish population. Gene dosage effect is not observed. The frequent de novo mutations found in the female patients are likely resulting from mutagenesis of X chromosome in paternal germ cells. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/23079138/Novel_and_de_novo_PHEX_mutations_in_patients_with_hypophosphatemic_rickets_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(12)01320-8 DB - PRIME DP - Unbound Medicine ER -