Are children of older fathers at risk for genetic disorders?
Are children of older fathers at risk for genetic disorders?
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DOI：
10.1046/j.1439-0272.2003.00579.x
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发表时间：
2003-08-01
期刊：
影响因子：
2.4
通讯作者：
Schill, WB
中科院分区：
文献类型：
--
作者：
Jung, A;Schuppe, HC;Schill, WB
与父亲年龄相关的遗传风险应该引起临床男科学家的兴趣，他们为希望生孩子的老年男性提供咨询。从理论上讲，精子发生过程中（减数分裂前）有丝分裂细胞分裂的数量以及与卵子发生相比随着年龄的增长而显着增加，将有利于老年男性后代的遗传风险。但是对于染色体数目和结构的异常，父亲年龄的影响还没有被发现，然而，在一些常染色体显性遗传疾病影响三个特定的基因（成纤维细胞生长因子受体2和3，RET原癌基因）的风险，一个孩子受到影响的父亲在出生时的年龄增加。对于其他常染色体显性- X染色体显性或隐性疾病，现有数据足以支持父亲年龄与新发基因突变之间存在正相关关系的概念。对受影响儿童及其父母的基因序列进行分析的研究将有助于进一步评估这一主题。然而，父亲年龄对具有复杂遗传背景的疾病的影响是一个有争议的问题。父亲年龄对非家族性阿尔茨海默病、先天性心脏病、非家族性精神分裂症、急性淋巴细胞白血病或前列腺癌没有显著影响。
Genetic risks related to paternal age should be of interest to clinical andrologists counselling older men who wish to father a child. Theoretically, the number of (pre-meiotic) mitotic cell divisions during spermatogenesis and their remarkable increase with ageing compared with oogenesis would be in favour of genetic risks for the offspring of older men. But for numerical and structural chromosomal anomalies, such an influence of paternal age has not been found. However, in several autosomal dominant disorders affecting three specific genes (fibroblast growth factor receptor 2 and 3, RET proto-oncogene) the risk for a child to be affected increases with paternal age at time of birth. For other autosomal dominant - X chromosomal dominant or recessive disorders, the available data are sufficient to support the concept of a positive relationship between paternal age and de novo gene mutations. Studies analysing gene sequences of affected children and their parents would allow further evaluation of this topic. The impact of paternal age on disorders with a complex genetic background, however, is a matter of debate. A significant effect of paternal age could not be shown for nonfamilial Alzheimer's disease, congenital heart defects, nonfamilial schizophrenia, acute lymphoblastic leukaemia or prostate cancer.