Improvement of molecular-genetic diagnostics of the most common skeletal dysplasias.

Unlabelled: achondroplasia (ACH) and hypochondroplasia (HCH) into the routine practice.

Background: Both disorders are usually caused by de novo gain-of-function type mutations in FGFR3 gene encoding the fibroblast growth factor receptor 3, which plays an important role in the metabolism of connective tissues. More than 99% of ACH cases are caused by the glycine-to-arginine substitution at codon 380 and about 70% of HCH cases result from the asparagine-to-lysine/-serine/-threonine substitutions at codon 540 in the consequence of the four different possible nucleotide changes occurred at the same codon.

Methods: Exons 10 and 13 of the FGFR3 gene were analysed by PCR-RFLP and sequencing analysis. The exon 13 sequencing was necessary for mutation type specification.

Results: We confirmed the diagnosis of ACH due to 1138G→A transition in 7 patients and we identified 1620C→A transversion responsible for HCH in 2 patients.

Conclusion: Due to serious limitations in recently used methods, we had to modify the molecular-genetic diagnostics approach. We developed the reliable diagnostics and made it available for achondroplasia and hypochondroplasia suspected patients (Tab. 1, Ref. 5, Ref. 17).