Limbic selectivity of clozapine
Limbic selectivity of clozapine
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DOI：
10.1016/s0140-6736(05)63079-6
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发表时间：
1997-08-16
期刊：
影响因子：
168.9
通讯作者：
Kerwin, RW
中科院分区：
文献类型：
--
作者：
Pilowsky, LS;Mulligan, RS;Kerwin, RW
以前不育的男性现在可以通过卵胞浆内精子注射（ICSI）繁殖，这引起了人们的担忧，即男性不育的遗传原因可能会遗传给ICSI衍生的后代。男性不育与几种遗传异常有关，如组成性染色体异常、Y染色体亚显微缺失和囊性纤维化跨膜传导调节因子（CFTR）基因突变。1在我们的男科诊所，我们在一系列连续的男性中对这三个变量进行了遗传筛查，这些男性的活动精子细胞少于1106个/mL，这是荷兰使用ICSI的入选标准。包括少精子症（n= 69）和无精子症（n= 11）男性。对所有患者进行核型分析，并对一个连续亚组（n= 58）进行Y染色体缺失和CFTR突变检测。我们在80例患者中发现7例（8.8%）外周血淋巴细胞核型异常，比总体发病率0.85%高10倍2（p<0.001，2检验;表）。我们分析了Y染色体缺失的多重PCR系统与标记的AZF-a，AZF-b，和AZF-c区域。3在58例患者中，有3例（5%）发现了与无精子症（DAZ）基因缺失相关的AZF-c缺失，标记sY 254和sY 255。在100名有生育能力的男性对照的研究中，用该测定法未检测到AZF缺失。3检测了13种常见的CFTR突变（F508、A455 E、G542 X、1717-1G-A、R553 X、R1162 X、N1303 K、W1282 X、3659 delC、E60 X、R117 H、F508 C（S1251 N））。在59名患者中有8名（14%）发现了单一突变，比估计的所有CFTR突变的群体发生率3.1%高出4倍（p<0.001）。4在3例患者中，CFTR突变与输精管结构异常（先天性双侧输精管缺失）相关，但在5例患者中存在输精管。在后一组中，1例仅支持细胞综合征患者同时出现AZF 508突变和AZF-c缺失。在我们的研究中，26%的男性存在与不孕症相关的遗传风险因素。在这些情况下使用ICSI可能会导致后代染色体互补不平衡的风险增加，由于Y连锁传播AZF缺失导致男性不育，5和一种囊性纤维化，需要对伴侣进行CFTR突变测试和夫妇的遗传咨询。我们的结论是，所有患有特发性少精子症或无精子症的不育男性在考虑ICSI之前都应该进行基因检测和遗传咨询。男性不育。柳叶刀1997; 349：787-90. 2尼尔森J，沃勒特M.阿胡斯一项13年发病率研究的结果显示，在34910名新生儿中发现了染色体异常。Genet 1991; 87：81-83.
That previously infertile men may now reproduce through intracytoplasmic sperm injection (ICSI) has raised concern that genetic causes of male infertility may be transmitted to the ICSI-derived offspring. Male infertility is associated with several genetic abnormalities such as constitutive chromosome abnormalities, submicroscopic deletions of the Y chromosome, and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. 1 At our andrology clinic, we carried out genetic screening for these three variables in a consecutive series of men with less than 1106 motile sperm cells per mL, the inclusion criterion for the use of ICSI in the Netherlands. Both oligozoospermic (n= 69) and azoospermic (n= 11) men were included. All patients were karyotyped, and a consecutive subgroup (n= 58) was also tested for Y-chromosomal deletions and CFTR mutations. We found an abnormal karyotype in peripheral blood lymphocytes in seven (8· 8%) of 80 patients, ten-fold more than the overall population incidence of 0· 85% 2 (p< 0· 001, 2 test; table). We analysed Y-chromosomal deletions with a multiplex PCR system with markers for the AZF-a, AZF-b, and AZF-c regions. 3 With markers sY254 and sY255, three (5%) of 58 patients were found to have an AZF-c deletion associated with the deleted-in-azoospermia (DAZ) gene. No AZF deletions were detected with this assay in a study of 100 fertile male controls. 3 We tested for 13 common CFTR mutations (∆ F508, A455E, G542X, 1717-1G-A, R553X, R1162X, N1303K, W1282X, 3659delC, E60X, R117H, F508C (S1251N). A single mutation was found in eight (14%) of 59 patients, four-fold more than the estimated population rate of all CFTR mutations of 3· 1%(p< 0· 001). 4 In three patients, the CFTR mutation was associated with a structural abnormality of the vas deferens (congenital bilateral absence of the vas deferens), but in five cases the vas deferens was present. In this latter group, one patient with Sertoli cell-only syndrome presented with both a∆ F508 mutation and an AZF-c deletion. 26% of the men in our study presented with a genetic risk factor associated with infertility. The use of ICSI in these cases may lead to offspring with an increased risk of an unbalanced chromosome complement, male infertility due to the Y-linked transmission of an AZF deletion, 5 and a form of cystic fibrosis, necessitating testing of their partners for CFTR mutations and genetic counselling of the couple. We conclude that all infertile men with idiopathic oligozoospermia or azoospermia should be offered genetic testing and genetic counselling before ICSI is considered.1 de Kretser DM. Male infertility. Lancet 1997; 349: 787–90. 2 Nielsen J, Wohlert M. Chromosome abnormalities found among 34910 newborn children, results from a 13-year incidence study in Arhus. Hum Genet 1991; 87: 81–83.