Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy

Spada, Albert R. La; Wilson, Elizabeth M.; Lubahn, Dennis B.; Harding, A. E.; Fischbeck, Kenneth H.

doi:10.1038/352077a0

Cited by 2,548 publications

(1,338 citation statements)

References 14 publications

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“…Primer pairs and amplification conditions were as described in previous reports. Trinucleotide repeats comprised: DM-1 (Brook et al, 1992), SCA-1 (Orr et al, 1993) and AR (La Spada et al, 1991). Dinucleotide repeats were: X75b (Jansen et al, 1992), a (TA)n repeat in the upstream region of the human oestrogen receptor gene (ERTA) (Del Senno et al, 1992), D6S193 (Saito et al, 1992), D16S289 (Shen et al, 1992), D16S400, D16S402 and D16S413 (Weissenbach et al, 1992).…”

Section: Tissuesmentioning

confidence: 99%

Microsatellite instability in early sporadic breast cancer

Shaw

Walsh²,

Chappell³

et al. 1996

Br J Cancer

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Summary We have studied the incidence of microsatellite instability at three trinucleotide repeats and seven dinucleotide repeats from five chromosomal regions, in a group of 30 mammographically detected 'early' invasive breast cancers and correlated its occurrence with clinicopathological parameters. The myotonic dystrophy (DM-1) trinucleotide repeat was analysed in 48 additional cases. In 4 out of 78 (5%) paired tumour-normal DNA samples we found evidence of somatic microsatellite instability at DM-1: a novel allele of a different size was seen in the tumour DNA which was not present in the normal DNA sample. All four tumours that showed evidence of instability were from the core group of 30 cases (13%) and were well or moderately differentiated, oestrogen receptor-positive, infiltrating ductal carcinomas. Two of these tumours were unstable at nine of ten loci studied, both trinucleotide and dinucleotide repeats. DNA prepared from different normal tissues showed no evidence of instability, for all four instability cases. These data indicate that microsatellite instability is specific to the tumour DNA and is an early event in the genesis of some sporadic breast cancers.

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Section: Tissuesmentioning

confidence: 99%

Microsatellite instability in early sporadic breast cancer

Shaw

Walsh²,

Chappell³

et al. 1996

Br J Cancer

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“…Hence, it's not difficult to understand that shorter CAG repeats, increasing AR activity, are associated with prostate cancer [15,16], hirsutism [17] and hyperandrogenism in ovary [18,19], while longer CAG repeats, decreasing AR activity, are related to hypoandrogenicity [20] and male infertility due to impaired sperm production [10,21]. CAG tracts beyond the normal range (>40 CAG repeats) leads to Kennedy's syndrome, a fatal neuromuscular disease [22].…”

Section: Introductionmentioning

confidence: 99%

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis

Peng

Xie

Guo

et al. 2014

J Assist Reprod Genet

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Purpose Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship. Methods 224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG) n repeat alleles. A metaanalysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate. Results We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65±2.5 vs. 23.09±2.1, P=0.116). When CAG bi-allelic were divided into two categories (mean repeats ≤22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25 % vs 29.14 %, P<0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3±2.5 vs. 23.9±2.2, P= 0.008) and long bi-allelic lengths (24.3±1.4 vs. 25.9±1.6, P= 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r=0.237, P=0.008), which accorded with our meta-analysis results. Conclusions The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.

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“…The triplet repeats in these diseases are expanded to as many as several hundred to several thousand repeat units. Expansion of CAG repeats in protein coding regions was first identified as the causative gene for spinal and bulbar muscular atrophy (SBMA) (La Spada et al, 1991). Since then expansion of CAG repeats in protein coding regions has been identified in Huntington's disease (HD) (The Huntington's Disease Collaborative Research Group, 1993), spinocerebellar ataxia type 1 (SCA1) (Orr et al, 1993), dentatorubral-pallidoluysian atrophy (DRPLA) (Koide et al, 1994;Nagafuchi et al, 1994a) and Machado-Joseph disease (MJD) (Kawaguchi et al, 1994) (Fig.…”

Section: Four Classes Of Triplet Repeat Diseases Classified Based On mentioning

confidence: 99%

“…As mentioned above, to date five diseases have been identified to be caused by unstable expansion of CAG repeats including SBMA, HD, SCA1, DRPLA and MJD (La Spada et al, 1991;The Huntington's Disease Collaborative Research Group, 1993;Orr et al, 1993;Koide et al, 1994;Nagafuchi et al, 1994a;Kawaguchi et al, 1994). The mode of inheritance of these diseases is autosomal dominant one except for SBMA which is inherited as an X-linked recessive trait.…”

Section: Expansion Of Ca G Repeats In Coding Region As a Common Mechamentioning

confidence: 99%

Unstable expansion of triplet repeats as a new disease mechanism for neurodegenerative diseases

Tsuji

1996

Jap J Human Genet

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IntroductionNeurodegenerative diseases have been defined as diseases characterized by gradual loss of neurops in particular regions of the central nervous system due to "unknown" causes. Substantial number of neurodegenerative diseases exhibit familial occurrence, suggesting that mutations in the causative genes are the primary cause of the diseases. Application of the molecular genetic strategy of "positional cloning" has enabled us to identify the causative genes without prior knowledge of the pathophysiology of the diseases. Among the causative genes which have been identified by the strategy of positional cloning, unstable expansions of triplet repeats have recently been discovered to be a common novel disease mechanism for neurodegenerative diseases. In this review I will focus on recent developments in the research on triplet repeat diseases with particular emphasis on non-Mendelian aspects of triplet repeat diseases.

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Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy

Cited by 2,548 publications

References 14 publications

Microsatellite instability in early sporadic breast cancer

Microsatellite instability in early sporadic breast cancer

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis

Unstable expansion of triplet repeats as a new disease mechanism for neurodegenerative diseases

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