Cell
Volume 78, Issue 2, 29 July 1994, Pages 335-342
Journal home page for Cell

Article
Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia

https://doi.org/10.1016/0092-8674(94)90302-6Get rights and content

Abstract

Achondroplasia (ACH) is the most common genetic form of dwarfism. This disorder is inherited as an autosomal dominant trait, although the majority of cases are sporadic. A gene for ACH was recently localized to 4p 16.3 by linkage analyses. The ACH candidate region includes the gene encoding fibroblast growth factor receptor 3 (FGFR3), which was originally considered as a candidate for the Huntington's disease gene. DNA studies revealed point mutations in the FGFR3 gene in ACH heterozygotes and homozygotes. The mutation on 15 of the 16 ACH-affected chromosomes was the same, a G→A transition, at nucleotide 1138 of the cDNA. The mutation on the only ACH-affected chromosome 4 without the G→A transition at nucleotide 1138 had a G→C transversion at this same position. Both mutations result in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3.

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    These authors contributed equally to this work.

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