The contribution of a novel PHEX gene mutation to X-linked hypophosphatemic rickets: a case report and an analysis of the gene mutation dosage effect in a rat model.

A Chinese family was identified to have two patients with rickets, an adult female and a male child (proband), both exhibiting signs related to X-linked hypophosphatemic rickets (XLH). Gene sequencing analysis revealed a deletion of adenine at position 1985 (c.1985delA) in the PHEX-encoding gene. To investigate the relationship between this mutation and the pathogenicity of XLH, as well as analyze the effects of different dosages of PHEX gene mutations on clinical phenotypes, we developed a rat model carrying the PHEX deletion mutation. The CRISPR/Cas9 gene editing technology was employed to construct the rat model with the PHEX gene mutation (c.1985delA). Through reproductive procedures, five genotypes of rats were obtained: female wild type (X/X), female heterozygous (-/X), female homozygous wild type (-/-), male wild type (X/Y), and male hemizygous (-/Y). The rats with different genotypes underwent analysis of growth, serum biochemical parameters, and bone microstructure. The results demonstrated the successful generation of a stable rat model inheriting the PHEX gene mutation. Compared to the wild-type rats, the mutant rats displayed delayed growth, shorter femurs, and significantly reduced bone mass. Among the female rats, the homozygous individuals exhibited the smallest body size, decreased bone mass, shortest femur length, and severe deformities. Moreover, the mutant rats showed significantly lower blood phosphorus concentration, elevated levels of FGF23 and alkaline phosphatase, and increased expression of phosphorus regulators. In conclusion, the XLH rat model with the PHEX gene mutation dosage demonstrated its impact on growth and development, serum biochemical parameters, and femoral morphology.

Be aware of the effects of glucocorticoids on SIADH: A case report.

RATIONALE: Hyponatremia is one of the most common electrolyte disorders in clinic. Due to the complicated etiology and the nonspecific clinical manifestations, the diagnosis of hyponatremia is a complicated process. A variety of clinical disorders can cause inappropriately increased antidiuretic hormone (ADH) secretion, leading to inappropriate water retention and consequent hyponatremia. The most common cause of hyponatremia in hospital inpatients is syndrome of inappropriate antidiuretic (SIADH). The action of glucocorticoid against pituitary posterior lobe can reduce the secretion of ADH. However, the effect of hormone on diuretic hormone during treatment has been less reported. PATIENT CONCERNS AND DIAGNOSIS: The patient in this case report was misdiagnosed as anterior pituitary hypofunction because of the long-term glucocorticoid therapy was effective in this patient, and the patient was finally diagnosed as SIADH after reassessment. The patient is a 76-year-old male with long-term symptomatic hyponatremia after traumatic brain injury (TBI). The patient has been consistently diagnosed as anterior pituitary hypofunction. Based on the diagnosis, glucocorticoid replacement therapy was administered. The serum sodium of the patient gradually increased to normal level after hydrocortisone intravenous injection but dropped again after switch to hydrocortisone oral administration. Through examination and analysis of the patient status during the five-time hospitalization, syndrome of inappropriate antidiuretic hormone (SIADH) was considered. INTERVENTIONS: Water intake limitation and oral furosemide and antisterone were administered after glucocorticoid therapy was stopped. OUTCOME: The serum sodium level of the patient gradually increased and maintained within normal range based on his clinical follow-up. LESSONS: For hyponatremia with effective glucocorticoid treatment, SIADH should still be excluded.