Lilford R, Jones A M, Bishop D T, Thornton J, Mueller R
Department of Clinical Medicine, University of Leeds.
BMJ. 1994 Sep 3;309(6954):570-3. doi: 10.1136/bmj.309.6954.570.
To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause.
Case-control study and segregation analysis.
Two teaching hospitals in Leeds.
Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department.
The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers.
Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families.
Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.
检验男性生育力低下具有家族性这一假设，并研究家族内生育力低下的分布情况，以确定其是否符合遗传病因。
病例对照研究和分离分析。
利兹的两家教学医院。
病例（先证者）为精子计数异常且前往生育力低下诊所就诊、其伴侣无重大生育相关因素的男性。对照为通过输精管切除术诊所或妇产科招募的有两个或更多孩子的父亲。
有伴侣的兄弟以及姐妹和二级、三级男性亲属中自然不育的发生率。尽可能从自然不育的兄弟处获取临床和实验室详细信息。
先证者的148名兄弟中有17名（11.5%）因不育寻求过医疗建议，而对照的169名兄弟中无人因不育寻求过医疗建议（P<0.0005）。4名先证者有不止1名自然不育的兄弟。另有6名兄弟的不育被认为是自然发生的，使先证者兄弟中生育力低下的总患病率达到16%。分离分析结果符合常染色体隐性遗传模式，该模式可解释男性生育力低下的60%。先证者的346名叔伯中有17名（4.9%）被报告自然不育，对照的420名叔伯中有10名（2.8%）被报告自然不育（P=0.09），但姐妹中的不育情况无差异。在3个家庭中，“患病”兄弟的精子计数证实了诊断，且显示出家庭内部而非家庭之间有相当大的相似性。
男性生育力低下具有家族性因素，观察结果表明超过半数的病例符合常染色体隐性遗传模式。可能涉及几个不同的基因。
