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).