Clinical, hormonal, biochemical and genetic characteristics of 75 patients with hypophosphatemic rickets

Abstract

Aim — the present research was aimed at identifying the genetic causes for hr in patients, as well as evaluating the clinical, hormonal and biochemical characteristics of the disease in this group of patients.Material and methods. 75 patients (aged, of 3 months to 57 years; females, n=38; males, n=37) with clinical and radiological findings of rickets, low serum phosphate and low tubular reabsorption of phosphate were included. ‘rickets panel’ genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). The panel included primers for multiplex amplification of 22 genes associated with genetic calcium metabolism dysfunctions. Bioinformatic analysis was performed using torrent suite (Ion Torrent) and ANNOVAR software packages.Results. Out of the 75 patients 36 were diagnosed with familial form of hr, and 39 probands had sporadic cases. Out clinical characteristics the most widespread symptoms of the disease included: lower limbs malformations since the patients started to walk (94.5%), hypotonia in the first 12 months of life (70.2%), multiple caries (58%). Mutations were identified in 100% of familial and 88,5% of sporadic cases. In 68 probands (90,5%) mutations were detected in PHEX, 40 of which were novel. For familial forms of the disease mutations were discovered in 100% cases, for sporadic — in 82% cases. One subject had both DMP1 and PHEX mutations. No mutations were detected in FGF23, SLC34A1, SLC34A3, SLC9A3R1, ENPP1, CLClCN5 and SLC2A2 genes.Conclusion. The study confirmed predominance of PHEX mutations among the patients with HR. The identification of causative agent is very important for antenatal diagnostics for familial forms of disease and enables well-timed conservative treatment.