Dataset Information

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan.

ABSTRACT:

Abstractintroductionandimportance

Autosomal dominant hypophosphatemic rickets is the most common form of rare rickets, commonly manifests in children but sometimes the condition remains undiagnosed due to lack of knowledge &/or awareness of treating physicians or surgeons.

Case presentation

We describe a case of 43 years old female with multiple fragility fractures since childhood, corrected surgically but never investigated. She had stunted growth, bowing deformities and loss of teeth.

Clinical discussion

A detailed history and examination along with metabolic and genetic work up mounted the diagnosis of X linked hypophosphatemic osteomalacia. The pathophysiology involves the mutation or the loss of the phosphate regulating gene on PHEX, that causes reduced mineralization of bones and teeth.

Conclusion

Diagnostic delay in this patient resulted in increased disabilities affecting her mobility and lif estyle.

SUBMITTER: Zehra N

PROVIDER: S-EPMC7840437 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan.

Zehra Nawazish N Jafri Lena L Kirmani Salman S Khan Aysha Habib AH

Annals of medicine and surgery (2012) 20210122

<h4>Abstractintroductionandimportance</h4>Autosomal dominant hypophosphatemic rickets is the most common form of rare rickets, commonly manifests in children but sometimes the condition remains undiagnosed due to lack of knowledge &/or awareness of treating physicians or surgeons.<h4>Case presentation</h4>We describe a case of 43 years old female with multiple fragility fractures since childhood, corrected surgically but never investigated. She had stunted growth, bowing deformities and loss of ...[more]

PMID: 33537138

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Project description:BACKGROUND:X-linked hypophosphatemic rickets (XLH) is a heterogeneous genetic phosphate wasting disorder that occupies the majority of inheritable hypophosphatemic rickets (HR). XLH is caused by loss-of-function mutations in the phosphate-regulating endopeptidase gene (PHEX) located on the X chromosome. METHOD:In this study, we performed whole-exome sequencing (WES) on the proband to identify the causative gene. The mutations were analyzed by predictive online software, such as PolyPhen-2. Plasmids containing the wild-type (WT) and mutant cDNA of the candidate gene were transfected into HEK293, then, the expression, cellular localization, and glycosylation state of the candidate proteins were detected by western blot, immunostaining, and endoglycosidase H digestion. The expression and concentration of related factor were measured by RT-PCR and ELISA. RESULTS:We identified a novel missense mutation c.2179T>C in the PHEX that results in the substitution of p.Phe727Leu (F727L). This mutation was predicted to be disease-causing by all four predictive online software. In vitro studies demonstrated that the F727L substitution hindered the intracellular trafficking of the mutant PHEX, with ~59% of mutant PHEX protein retained in the endoplasmic reticulum (ER) and only ~16% of the mutant protein localized on the cell surface. Endoglycosidase H digestion assay showed that the mutant F727L PHEX protein was not fully glycosylated. The concentration of intact FGF23 in hFOB1.19 cell culture medium collected from the mutant PHEX group was the highest (62.9 pg/ml) compared to the WT group (32.1 pg/ml) and control group (23.5 pg/ml). CONCLUSION:Our results confirmed that the mutant PHEX protein was lowly glycosylated and retarded within the ER, the intact FGF23 level in cell culture media caused by the mutant PHEX protein was significantly elevated compared to that of the WT group, which may explain why the single base mutation in the PHEX led to XLH syndrome in this family.

Dataset Information

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan.

Abstractintroductionandimportance

Case presentation

Clinical discussion

Conclusion

Publications

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan.

Similar Datasets

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