Ikegawa S, Fukushima Y, Isomura M, Takada F, Nakamura Y
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Hum Genet. 1995 Sep;96(3):309-11. doi: 10.1007/BF00210413.
Achondroplasia, the most common cause of chondrodysplasia in man, is characterized by short-limbed dwarfism, macrocephaly, and dysplasia of metaphyses of the tubular bones. Recently, mutations in the gene encoding fibroblast growth factor receptor-3 (FGFR-3) have been found in patients with achondroplasia. All mutations so far reported had occurred at codon 380, resulting in the substitution of an arginine for a glycine in the transmembrane domain of the predicted protein. We have examined the transmembrane domain of the FGFR-3 gene in seven Japanese patients with achondroplasia. Of the six cases that were sporadic, all carried a mutation in codon 380; the single familial case bore a novel mutation of a G-to-T transition at codon 375, which resulted in substitution of a cysteine for a glycine.
软骨发育不全是人类软骨发育异常最常见的原因，其特征为四肢短小性侏儒症、巨头畸形以及管状骨干骺端发育异常。最近，在软骨发育不全患者中发现了编码成纤维细胞生长因子受体-3（FGFR-3）的基因突变。迄今报道的所有突变均发生在第380密码子，导致预测蛋白质跨膜结构域中的甘氨酸被精氨酸取代。我们检测了7例日本软骨发育不全患者的FGFR-3基因跨膜结构域。在6例散发病例中，均携带第380密码子的突变；唯一的1例家族病例在第375密码子发生了新的G-to-T转换突变，导致甘氨酸被半胱氨酸取代。
