Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies.
OBJECTIVE
To evaluate the influence of aging on the achondroplasia mutation rate in the male germline.


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


METHODS
University teaching hospital.


METHODS
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.


METHODS
Testes were obtained from 14 deceased donors, and sperm was obtained from 17 patients who requested ART.


METHODS
Real-time polymerase chain reaction quantification of the G1138A mutation in sperm and testis biopsies.


RESULTS
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.


CONCLUSIONS
These findings could contribute to providing a molecular explanation for the increased incidence of achondroplastic offspring with advanced paternal age.
Dakouane Giudicelli
Mbarka
M
Unité de Pathologie Cellulaire et Génétique, Université Versailles Saint-Quentin, Faculté de Médecine Paris-Ile-de-France-Ouest and Centre Hospitalier de Poissy-Saint Germain, Poissy, France. dakouane@hotmail.com
Serazin
Valerie
V
Le Sciellour
Christelle Rouillac
CR
Albert
Martine
M
Selva
Jacqueline
J
Giudicelli
Yves
Y
D000130:Achondroplasia / Q000235:genetics*; D000225:Adenine; D000328:Adult; D000368:Aged; D001706:Biopsy; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005787:Gene Frequency; D006147:Guanine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D015183:Restriction Mapping; D013737:Testis / Q000166:cytology / Q000473:pathology*
D006147:Guanine; D012313:RNA; D004247:DNA; D000225:Adenine