TY - JOUR
T1 - Imprinting effect in premature ovarian failure confined to paternally inherited fragile X premutations
AU - Hundscheid, Rubin D.L.
AU - Sistermans, Erik A.
AU - Thomas, Chris M.G.
AU - Braat, Didi D.M.
AU - Straatman, Huub
AU - Kiemeney, Lambertus A.L.M.
AU - Oostra, Ben A.
AU - Smits, Arie P.T.
N1 - Funding Information: We would like to thank all the women who participated in this study, Prof. Hans M. W. M. Merkus for his support, and Meyke Schouten for data processing and statistical assistance. The expert technical assistance of the laboratory technicians and the help of the secretaries are acknowledged. The Zorg Onderzoek Nederland Foundation is acknowledged for financial support. Thanks also to Prof. Han G. Brunner for critically reading the manuscript.
PY - 2000
Y1 - 2000
N2 - Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in female carriers. The occurrence of POF and age at menopause in women with a paternally inherited fragile X premutation (PIP) were compared to those in women with a maternally inherited fragile X premutation (MIP). We identified 148 women in whom the parental origin of the premutation could be determined. In 109 of these women we were able to establish whether POF had occurred: 82 women had a PIP, and 27 had a MIP. Twenty-three of the women (28%) with a PIP had POF, versus only 1 (3.7%) with a MIP (two-tailed Fisher's exact test; P = .007). Kaplan-Meier analysis of all 148 premutations showed that the age at menopause was significantly lower in the women with a PIP than in the woman with a MIP (Breslow test in Kaplan- Meier analysis; P = .003). Our data strongly suggest that, when POF occurs in fragile X premutation carriers, a considerable proportion of the premutations are inherited paternally (parent-of-origin effect). We hypothesize that this may be owing to a paternal genomic imprinting effect.
AB - Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in female carriers. The occurrence of POF and age at menopause in women with a paternally inherited fragile X premutation (PIP) were compared to those in women with a maternally inherited fragile X premutation (MIP). We identified 148 women in whom the parental origin of the premutation could be determined. In 109 of these women we were able to establish whether POF had occurred: 82 women had a PIP, and 27 had a MIP. Twenty-three of the women (28%) with a PIP had POF, versus only 1 (3.7%) with a MIP (two-tailed Fisher's exact test; P = .007). Kaplan-Meier analysis of all 148 premutations showed that the age at menopause was significantly lower in the women with a PIP than in the woman with a MIP (Breslow test in Kaplan- Meier analysis; P = .003). Our data strongly suggest that, when POF occurs in fragile X premutation carriers, a considerable proportion of the premutations are inherited paternally (parent-of-origin effect). We hypothesize that this may be owing to a paternal genomic imprinting effect.
UR - http://www.scopus.com/inward/record.url?scp=0033912299&partnerID=8YFLogxK
U2 - https://doi.org/10.1086/302774
DO - https://doi.org/10.1086/302774
M3 - Article
C2 - 10677300
SN - 0002-9297
VL - 66
SP - 413
EP - 418
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -