J Genet Med.  2022 Jun;19(1):27-31. 10.5734/JGM.2022.19.1.27.

A novel variant of PHEX in a Korean family with X-linked hypophosphatemic rickets

  • 1Departments of Pediatrics, Dong-A University Hospital, Busan, Korea
  • 2Departments of Orthopedic Surgery, Dong-A University Hospital, Busan, Korea
  • 3Departments of Laboratory Medicine, Dong-A University Hospital, Busan, Korea


X-linked dominant hypophosphatemic rickets are the most common form of familial hypophosphatemic rickets resulting from hypophosphatemia caused by renal phosphate wasting, which in turn is a result of loss-of-function mutations in PHEX. Herein, we report a 39-year-old female with short stature and skeletal deformities and 12-month-old asymptomatic daughter. The female has a history of multiple surgical treatments because of lower limb deformities. Her biochemical findings revealed low serum phosphorus levels with elevated serum alkaline phosphatase activity and normal serum calcium levels, suggesting presence of hypophosphatemic rickets. To identify the molecular causes, we used a multigene testing panel and found a mutation, c.667dup (p.Asp223GlyfsTer15), in PHEX gene. To the best of our knowledge, this is a novel mutation. A heterozygous form of the same variant was detected in daughter, who showed no typical symptoms such as bow legs, frontal bossing, or waddling gate, but presented early signs of impaired mineralization in both X-ray and biochemical findings. The daughter was initiated onto early medical treatment with oral phosphate supplementation and an active vitamin D analog. Because the daughter was genetically diagnosed based on a family history before the onset of symptoms, appropriate medical management was possible from early infancy.


Familial hypophosphatemic rickets; Genetic testing; Genetic counseling; High-throughput nucleotide sequencing
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