Summary

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

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FGFR3 = fibroblast growth factor receptor 3