A case report of X-Linked Hypophosphatemic Rickets (XLHR) with a novel mutation in the PHEX gene

Introduction and Aim X-linked hypophosphatemic rickets, inherited in a dominant manner, is the most commonform of familial hypophosphatemic rickets. Clinical manifestations of XLHR can vary but most patients willpresent with limb deformity, primarily affecting the legs and short stature. A 2-year-old boy presented to uswith a complaint of curvature of the legs. Physical examination revealed pectus carinatum and genu varumdeformity. His mother had short stature and hypochondroplasic-disproportional body view. Biochemical bloodmeasures were as follows: ALP:827 U/L, iP:2.6 mg/dL, PTH:107.1 pg/mL, calcium:10.37 mg/dL. We aimed tocontribute to the literature by sharing the novel mutation of PHEX gene we found in our case. Material andMethod With peripheral blood sample, the FGFR3 and PHEX genes were analyzed by sequence analysis andnext generation sequencing (NGS) method respectively. Results FGFR3 gene sequence analysis revealed aheterozygous c.1082-13C>T alterati n in the intr n 8, near the ‘’splice site’’. His m ther had the samealteration; his brother without symptoms also had the mutation. Later, PHEX gene analysis revealed ahemizygous c.436+1G>T splice donor novel mutation in the intron 4. Discussion The phenotypic spectrum ofXLHR ranges from isolated hypophosphatemia to severe lower-extremity bowing. The clinic of our case wascompatible with this disease. Initially, the alteration in the FGRF3 gene suggested that it could not causephenotype in our case because it was detected in the healthy brother. By showing a novel mutation in the PHEXgene, we highlighted the diagnosis of XLHR.KEYWORDS: PHEX, hypophosphatemic rickets , NOVEL, NGS