<unk>  is associated with a mutation in the PHEX gene sequence, located on the human X chromosome at location Xp22.2-p22.1. The PHEX protein regulates another protein called fibroblast growth factor 23 (produced from the FGF23 gene). Fibroblast growth factor 23 normally inhibits the kidneys' ability to reabsorb phosphate into the bloodstream. Gene mutations in PHEX prevent it from correctly regulating fibroblast growth factor 23. The resulting overactivity of FGF-23 reduces vitamin D 1α-hydroxylation and phosphate reabsorption by the kidneys, leading to<unk>  and the related features of hereditary<unk>  rickets. Also in<unk> , where PHEX enzymatic activity is absent or reduced, osteopontin—a mineralization-inhibiting secreted substrate protein found in the extracellular matrix of bone—accumulates in bone (and teeth) to contribute to the osteomalacia (and odontomalacia) as shown in the mouse homolog (Hyp) of<unk>  and in<unk>  patients. Biochemically in blood,<unk>  is recognized by<unk>  and an inappropriately low level of calcitriol (1,25-(OH)2 vitamin D3). Patients often have bowed legs or knock knees in which they usually cannot touch both knees and ankles together at the same time. The disorder is inherited in an X-linked dominant manner. This means the defective gene responsible for the disorder (PHEX) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity in males than females. As the X chromosome is one of the sex chromosomes (the other being the Y chromosome), X-linked inheritance is determined by the sex of the parent carrying a specific gene and can often seem complex. This is because, typically, females have two copies of the X-chromosome and males have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.
X-linked hypophosphatemia
Autosomal dominant hypophosphatemic rickets
Pseudohypoparathyroidism
X-linked recessive hypoparathyroidism
Eruptive hypomelanosis
Hypoparathyroidism
Malignant infantile osteopetrosis
Pseudopseudohypoparathyroidism