TY - JOUR
T1 - Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome
AU - Wilkin, Douglas J.
AU - Szabo, Jinny K.
AU - Cameron, Rhoda
AU - Henderson, Shirley
AU - Bellus, Gary A.
AU - Mack, Michelle L.
AU - Kaitila, Ilkka
AU - Loughlin, John
AU - Munnich, Arnold
AU - Sykes, Bryan
AU - Bonaventure, Jacky
AU - Francomano, Clair A.
N1 - Funding Information:
The authors wish to thank Iain McIntosh, Ph.D., for helpful discussions; Margaret Abbott, R.N., for collecting clinical information; and Dr. Marek Sanak, for referring families. The authors also would like to thank the patients and their families for participating in this study. This study was supported, in part, by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health; by European Union grant BMH1-CT93-1316; and by a grant from the Association Française des Myopathes.
PY - 1998/9
Y1 - 1998/9
N2 - 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.
AB - 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.
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U2 - 10.1086/302000
DO - 10.1086/302000
M3 - Article
C2 - 9718331
AN - SCOPUS:0032231407
SN - 0002-9297
VL - 63
SP - 711
EP - 716
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -