Ann Pediatr Endocrinol Metab.  2020 Mar;25(1):63-67. 10.6065/apem.2020.25.1.63.

Identification of a novel variant in the PHEX gene using targeted gene panel sequencing in a 24-month-old boy with hypophosphatemic rickets

• Jo HY
• Shin JH
• Kim HY
• Kim YM
• Lee H
• Bae MH
• Park KH
• Jang JH
• Kwak MJ

• KMID: 2501040
• DOI: http://doi.org/10.6065/apem.2020.25.1.63

Abstract

Familial hypophosphatemic rickets (FHR) is a disorder characterized by phosphate wasting and hypophosphatemia due to defects in renal phosphate transport regulation. There are 4 known inherited forms of FHR that differ in their molecular causes. Very few studies have been conducted that focused on the molecular analysis of FHR in Koreans. Eighteen mutations of the PHEX gene have been identified to this date in Korea. Herein, we report the clinical case of a 24-month-old boy presenting with bowed legs and short stature. The biochemical profile showed hypophosphatemia with decreased tubular reabsorption of phosphate. Several family members were identified with short stature and genu varum. Therefore, he was diagnosed with FHR. To identify the molecular causes of FHR, we performed targeted gene panel sequencing and found a novel hemizygous missense variant, c.1949T>C (p.Leu650Pro), in the PHEX gene. This variant was also detected in the boy’s mother who exhibited genu varum and short stature.

Keyword

Hypophosphatemic rickets; Mutation; Targeted gene panel sequencing

Figure

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  Fig. 1. (A) The patient’s photograph taken at the age of 2 years shows bowed legs. (B) A radiograph of the lower legs reveals diffuse bone contour changes as well as fraying and widening of the distal femoral metaphysis with varus deformity.

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  Fig. 2. Pedigree of the proband is consistent with a dominant mode of inheritance. The black symbols represent the affected individuals with short stature and genu varum. The asterisks (*) indicate the individuals who had undergone surgical correction for genu varum.

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  Fig. 3. Partial genomic DNA sequence of the patient and patient’s mother shows the c.1949T>C (p.Leu650Pro) variant in the PHEX gene.

Reference

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