Mutation screening and CAG repeat length analysis of the androgen receptor gene in Klinefelter's syndrome patients with and without spermatogenesis

BACKGROUND: Mutations of the androgen receptor (AR) gene give rise to a wide array of phenotypic abnormalities. A systematic analysis of the AR gene in patients with 47,XXY has not previously been performed. METHODS: Mutations of the AR gene and expansion of the CAG repeats in exon 1 of the AR gene were studied in 13 patients with Klinefelter's syndrome either with (n = 1) or without (n = 12) spermatogenesis. RESULTS: No abnormalities in the AR gene were detected by single strand conformational polymorphism analysis. The CAG lengths ranged from 17 to 27 (mean +/- SD 22.8 +/- 3.3, median 23) for Klinefelter patients or from 17 to 28 (mean +/- SD 23.2 +/- 2.6, median 23) for control subjects. X-inactivation analysis for the methylation status of the AR gene was performed in seven patients who were heterozygous for CAG repeats of different length, showing that the longer CAG repeat alleles underwent random but more frequent inactivation in five patients and skewed inactivation in two. CONCLUSIONS: An AR gene abnormality does not constitute an important factor for impaired spermatogenesis in patients with Klinefelter's syndrome.     

Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study

BACKGROUND: Recent data emphasized the implication of polymerase gamma (POLG) CAG repeats in infertility, making it a very attractive gene for study. A comparison of POLG CAG repeats in infertile and fertile men showed a clear association between the absence of the usual 10-CAG allele and male infertility, excluding azoospermia. It has also been suggested that the POLG gene polymorphism should be considered as a possible contributing factor in unexplained couple infertility where semen parameters are normal. In this study, we investigated the POLG CAG repeats, in a well-defined population of patients with severe male factor infertility. METHODS: We conducted a large study of POLG CAG repeats in 433 infertile and 91 fertile, normozoospermic and healthy males. In all subjects, phenotypic data, including semen parameters, hormonal status and clinical profiles, were available. RESULTS: Thirteen 'homozygous mutants' (3%) were found among the 433 idiopathic infertile patients. The follow-up of the 13 'homozygous mutant' resulted in pregnancy for more than half of the couples, through assisted reproductive techniques or even spontaneously. In addition, one 'homozygous mutant' was identified in 91 fertile men (1.1%) CONCLUSION: Under our conditions, our study does not confirm any relationship between the polymorphic CAG repeat in the POLG gene and male infertility.     

A patient homozygous for the SCA6 gene with retinitis pigmentosa

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.     

应用CAG方案治疗老年急性髓系白血病的疗效观察

目的探讨应用CAG方案治疗老年急性髓系白血病的效果.方法 选择老年性AML患者26例,均采取CAG方案治疗,两个疗程后观察疗效及不良反应.结果 26例患者中,完全缓解16例,部分缓解4例,总有效率为76.92%.大部分患者出现可耐受的骨髓抑制,未见有明显的心、肝、肾等脏器损害.结论 CAG方案疗效良好,不良反应发生率低且轻微,尤其对高龄、并发症多、对强化疗不能耐受的患者更为适用.     

北京万寿路地区319例男性AR基因(CAG)n重复序列多态的研究

目的研究自然人群中老年男性雄激素受体(AR)基因CAG重复序列多态。方法使用DNA测序方法对319例老年男性AR基因外显子1 NH2端转录调节区内CAG重复序列长度进行测定。结果男性雄激素受体基因CAG重复数最短为8,最长为35。CAG重复数平均值为(22．70 ±3．66)。CAG重复数分布频率最多的为21(13．8％),22(15．7％),23(13．5％)和24(10．3％),共占 53．3％。结论自然人群中老年男性雄激素受体基因CAG重复序列呈现多态性,多数集中在21- 24,为进一步研究AR基因变异与疾病的关系提供依据。     

Making Sense of Intratumor Genetic Heterogeneity: Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues

To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient‐matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 18–25 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t‐tests. These results suggest that preferential selection of 18–25 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.     

慢性萎缩性胃炎证候分布规律研究现状与思考

目的把握现阶段慢性萎缩性胃炎证候分布规律研究现状,为进一步开展该病的证候规范化、标准化研究提供有益指导。方法全面检索中国期刊全文数据库(CNKI)、重庆维普(VIP)及万方数据库自建库至2013年12月31日关于慢性萎缩性胃炎证候分布规律相关研究,纳入相关文献31篇进行分析。结果现阶段慢性萎缩性胃炎在流行病学资料、主要症状、常见证候类型及不同证候间微观辨证相关性方面取得了一定的成果。然而仍存在病例采集纳入排除标准不统一、病例来源地局限、样本量偏小、缺少相应的专家调研以及数据挖掘方法较单一的问题。结论慢性萎缩性胃炎证候分布规律当进行多中心、大样本、以大课题为支撑的研究,多学会联合形成统一的证候诊断标准更是该病中医规范化研究得以顺利进行的关键。