Achondroplasia is the most common short-limbed dwarfism in humans. In over 95% of cases the syndrome is caused by the same point mutation (G1138A) in FGF3R receptor in all patients. The nucleotide transition within transmembrane domain of this receptor tyrosine kinase changes glycine codon for arginine.

We studied one familial and 4 sporadic cases of achondroplasia, diagnosed in the first year of life on clinical features of rhizomelic short stature, frontal bossing and cranium. pelvic and femoral involvement in radiological examinations.

DNA studies were completed by PCR amplification method, with specific primers pairs flanking the transmembrane domain of FGFR3. The mutated alleles were detected by single strand conformation polymorphism (SSCP). The G1138A mutation was confirmed by endonuclease EcoNI digestion in three sporadic cases. In the other two cases further studies of FGF3R were done. Second region of interest, the proximal tyrosine kinase domain was amplified and tested by SSCP. A common mutation for hypochondroplasia. Asn540Lys was found in a familial case, in which affected mother and son were independently diagnosed achondroplasia on the clinical basis. In one case, no mutation has been found so far.

Our results confirm the predominance of G1138A mutation in achondroplasia, but challenge the link between molecular pathology and clinical picture of FGF3R mutations.