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The parental origin of 47,XXY males
J Harvey1, P A Jacobs, T Hassold
1Wessex Regional Genetics Laboratory, Salisbury General Hospital, Wiltshire, England.
Insights
The origin of the extra X chromosome in XXY males varies by ascertainment method. Maternal nondisjunction, particularly in meiosis I, is linked to advanced maternal age in referred cases.
Area of Science:
- Genetics
- Reproductive Biology
- Human Development
Background:
- Klinefelter syndrome (XXY) is a common sex chromosome aneuploidy.
- Understanding the parental origin of the extra X chromosome is crucial for genetic counseling.
Purpose of the Study:
- To determine the parental origin of the additional X chromosome in XXY males.
- To investigate the meiotic stage of nondisjunction in maternal cases.
- To explore the relationship between parental age and the origin of XXY.
Main Methods:
- DNA marker analysis to trace parental origin of the X chromosome.
- Ascertainment of XXY males through livebirth cytogenetic studies and clinical referrals.
- Analysis of meiotic errors in maternally derived XXY cases.
Main Results:
- In liveborn XXY males, 44% had a paternal X and 56% had a maternal X.
- In clinically referred XXY males, 54% had a paternal X and 46% had a maternal X.
- Maternal nondisjunction occurred in meiosis I (72%) or meiosis II (28%), with meiosis I errors linked to higher maternal age in referred cases.
Conclusions:
- The parental origin of the extra X chromosome in XXY males differs between population-based and clinically referred cohorts.
- Maternal nondisjunction in meiosis I is the predominant cause of maternally derived XXY, particularly in older mothers.
- No significant association between parental age and paternal X origin was observed.
Abstract:
We report the results of our investigation using DNA markers, of the parental origin of 61 XXY males ascertained during cytogenetic studies of consecutive liveborn babies and compare our results with those obtained from a study of 50 XXY males ascertained through clinical referral or amniocentesis. In the former group 44% of newborn XXY males obtained the additional X chromosome from their father and 56% from their mother, while in the latter "referral" group the additional X chromosome was paternally derived in 54% and maternally derived in 46% of the cases. The precise maternal cell division at which nondisjunction occurred was determined in 39 cases of maternal origin. Twenty eight (72%) resulted from an error in the first meiotic division and 11 (28%) from an error in the second meiotic division. There was no evidence of an origin due to a postzygotic mitotic error. There was no significant difference in the parental age at birth between those patients who received the additional X from their father and those who received it from their mother. However, those patients who received the additional X chromosome as a result of a maternal meiotic I error had a higher maternal age than any other category, but the difference reached a level of formal significance only for the clinically referred patients.