Molecular genetic testing of FGFR3 gene mutation in the differential diagnosis of achondroplasia and hypochondroplasia

  • І. М. Дмитрук
  • Г. В. Макух
  • М. Я. Тиркус
  • В. І. Шуварська
  • Н. В. Маркевич
  • О. В. Лялюк


Aims. The differential diagnosis of achondroplasia and hypochondroplasia in Ukraine is based on the typical clinical and radiologic features that limits accurate diagnosis and leads to many false-positive diagnoses when checked against a complete mutation search of the FGFR3 gene. Thereby, we outline the necessity of implementation molecular-genetic test of FGFR3 gene mutations. The implementation is necessary to carry out differential and prenatal diagnostic of achondroplasia and hypochondroplasia among Ukrainian population. Methods. The study included 62 patients with clinical things of achondroplasia or hypochondroplasia and 99 relatives including sibs and parents. The molecular-genetic analysis was performed by PCR (Polymerase Chain Reaction) and RFLP (Restriction Fragment Length Polymorphism) analysis. We optimized the time and temperature conditions and chose specific primers for revealing the c.1138G>A, c.1138G>C and p.Asn540Lys mutations of FGFR3 gene. Results. Mutation c.1138G>A was found at 21 (34 %) individuals aged from 5 months to 40 years old with obvious phenotypical features of achondroplasia of which 25 cases was sporadic. Additionally the mutation c.1138G>C was detected at 3 (5 %) probands. Major p.Asn540Lys mutation of the FGFR3 receptor was identified at 3 (5 %) probands which causes hypochondroplasia. Conclusions. We concluded that 93 % of mutations were sporadic because no mutations were found at relatives; meanwhile we found 2 (2 %) inheritable c.1138G>A and c.1138G>C mutations at both mother and son. Due to conducting of molecular-genetic diagnostics of FGFR3 mutations c.1138G>A, c.1138G>C and p.Asn540Lys diagnosis achondroplasia and hypochondroplasia were confirmed at 27 (44 %) observed patients and extensive gene analysis are required for the other patients to search for rare FGFR3 rearrangements.

Keywords: hypochondroplasia, achondroplasia, mutation, molecular-genetic diagnostics.