Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies

Fertil Steril. 2008 Jun;89(6):1651-6. doi: 10.1016/j.fertnstert.2007.04.037. Epub 2007 Aug 13.

Abstract

Objective: To evaluate the influence of aging on the achondroplasia mutation rate in the male germline.

Design: Studies in sperm and testis biopsy DNA according to donor's age.

Setting: University teaching hospital.

Patient(s): Seventeen donors aged 30 to 65 years for sperm collection and 14 deceased donors aged 53 to 95 years for testis biopsies, all with normal stature.

Intervention(s): Testes were obtained from 14 deceased donors, and sperm was obtained from 17 patients who requested ART.

Main outcome measure(s): Real-time polymerase chain reaction quantification of the G1138A mutation in sperm and testis biopsies.

Result(s): The rate of G1138A mutation did not significantly vary with age in sperm, whereas in testis biopsies it increased markedly past the age of 70 years. Moreover, and for the first time, a mosaic for this mutation was detected in the testis of three subjects who were >80 years of age.

Conclusion(s): These findings could contribute to providing a molecular explanation for the increased incidence of achondroplastic offspring with advanced paternal age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achondroplasia / genetics*
  • Adenine
  • Adult
  • Aged
  • Biopsy
  • DNA / genetics
  • DNA / isolation & purification
  • Gene Frequency
  • Guanine
  • Humans
  • Male
  • Middle Aged
  • Mosaicism*
  • Mutation*
  • Polymorphism, Single Nucleotide*
  • RNA / genetics
  • Reference Values
  • Reproducibility of Results
  • Restriction Mapping
  • Testis / cytology
  • Testis / pathology*

Substances

  • Guanine
  • RNA
  • DNA
  • Adenine