Korean J Clin Pathol.  2001 Apr;21(2):164-168.

Mutation analysis of Fibroblast Growth Factor Receptor 3 (FGFR3) Gene in Korean Patients with Achondroplasia and Hypochondroplasia

• Shin S
• Choi IH
• Cho TJ
• Ryang SW
• Yoon KY
• Kim J
• Park SS

Abstract

BACKGROUND
Achondroplasia is the most common form of dwarfism. The achondroplasia class consists of achondroplasia, thanatophoric dysplasia and hypochondroplasia. Clinical symptoms are variable, but the common gene, fibroblast growth factor receptor 3 (FGFR3), could account for these variable conditions. We tried to isolate the molecular defects in Korean patients with achondroplasia and hypochondroplasia.
METHODS
The sites frequently mutated (G380R and N540K) of the FGFR3 gene of seventeen Korean patients with skeletal dysplasia (16 cases of achondroplasia and one of hypochondroplasia) were analyzed by PCR-RFLP and confirmed by direct sequencing.
RESULTS
Missense mutations, which cause G380R of the FGFR3, were present in 15/16 (93.7%) achondroplasia patients. Among these, G to A transition was found in 14 of the 15 (93.3%) patients, and a G to C transversion in a single (6.6%) patient. One case did not show any mutation of the FGFR3 gene reported in achondroplasia, including G375C. A patient with suspected hypochondroplasia exhibited the common C to G transversion mutation, resulting in N540K.
CONCLUSIONS
The mutations at codons 380 and 540 of the FGFR3 gene were also found to be common causative mutations of achondroplasia and hypochondroplasia, respectively, in Koreans. These mutations could be used as the target of molecular diagnosis. Based on this simple molecular study, genetic counseling for skeletal dysplasia and prenatal diagnosis will be possible.

Keyword

Achondroplasia; Hypochondroplasia; FGFR3

MeSH Terms

Achondroplasia*
Codon
Diagnosis
Dwarfism
Fibroblast Growth Factors*
Fibroblasts*
Genetic Counseling
Humans
Mutation, Missense
Prenatal Diagnosis
Receptor, Fibroblast Growth Factor, Type 3*
Receptors, Fibroblast Growth Factor*
Thanatophoric Dysplasia
Codon
Fibroblast Growth Factors
Receptor, Fibroblast Growth Factor, Type 3
Receptors, Fibroblast Growth Factor