Screening for the presence of frequent pathogenic variants in the FGFR3 gene in patients with achondroplasia

Abstract

Achondroplasia is a congenital disease, the most common form of short-limb dwarfism, inherited by autosomal dominant type. The pathogenesis is based on a disruption of endochondral ossification. Patients exhibit short stature with shortening of the proximal parts of the limbs, facial abnormalities. Hypochondroplasia is much milder. Both disorders are causes by mutations in the FGFR3 gene. Achondroplasia is caused in 99% of cases by mutation c.1138G>A/C (p.Gly380Arg), 60% of hypochondroplasia is caused by variant c.1620C>A/G (p.Asn540Lys). The mutations leading to achondroplasia cause constitutive activation of FGFR3. Due to orthopedic and neurological complications, it is important to treat achondroplasia. Pharmacological treatment of the disease is being developed. Molecular genetic diagnosis of achondroplasia is relevant for the timely initiation of treatment. The paper presents the first results of selective screening program FSBI «RCMG» for the presence of frequent pathogenic variants in the FGFR3 gene. Based on the material of 270 patients the informativeness of the program was 70%. The share of the most frequent mutation р.Gly380Arg (c.1138G>A/С) account for 85.7%. A variant of р.Asn540Lys (c.1620C>A/G) was detected in 13.7% of cases.