Three Sporadic Cases of Achondroplasia average paternal age 35.86 all mutations FGFR-3 on paternally derived chromosome

this study was 35.86 years, suggesting an advanced
paternal age effect.


Mutations in Fibroblast Growth-Factor Receptor 3 in Sporadic Cases of Achondroplasia Occur Exclusively on the Paternally Derived Chromosome
Author(s) Douglas J. Wilkin, Jinny K. Szabo, Rhoda Cameron, Shirley Henderson, Gary A. Bellus, Michelle L. Mack, Ilkka Kaitila, John Loughlin, Arnold Munnich, Bryan Sykes, Jacky Bonaventure, and Clair A. Francomano
Identifiers The American Journal of Human Genetics, volume 63 (1998), pages 711–716
DOI: 10.1086/302000
PubMed ID: 9718331

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Copyright © 1998, The American Society of Human Genetics.
Abstract More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms were identified in the FGFR3 gene, within close proximity to the achondroplasia mutation site. Ninety-nine families, each with a sporadic case of achondroplasia in a child, were analyzed in this study. In this population, the achondroplasia mutation occurred on the paternal chromosome in all 40 cases in which parental origin was unambiguous. This observation is consistent with the clinical observation of advanced paternal age resulting in new cases of achondroplasia and suggests that factors influencing DNA replication or repair during spermatogenesis, but not during oogenesis, may predispose to the occurrence of the G1138 FGFR3 mutations.