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

  title={Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy},
  author={Albert R. La Spada and Elizabeth M. Wilson and Dennis B. Lubahn and Anita E. Harding and Kenneth H. Fischbeck},
X-LINKED spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely… 

Kennedy's disease: genetic diagnosis of an inherited form of motor neuron disease.

This study confirms this genetic mutation in 12 males from eight different families, ranging in age from less than one year to over 40 years of age, which was not found in five patients with other forms of motor neuron disease.

Polymorphic CAG repeat length in the androgen receptor gene and association with neurodegeneration in a heterozygous female carrier of Kennedy’s disease

It is hypothesized that the expression of the Kennedy’s disease mutation combined with a second allele with a large but normal CAG repeat sequence may have contributed to the motor neuron degeneration displayed in the heterozygote female and the possible reasons for phenotypic expression in particular individuals.

Men with Kennedy disease have a reduced risk of androgenetic alopecia

KD is an X‐linked neurodegenerative disease caused by an expansion of a polymorphic tandem CAG repeat within the androgen receptor (AR) gene on chromosomal locus Xq11‐q12 and degree of expansion of this repeat region is correlated with age at onset and disease severity.

X-linked recessive spina and bulbar muscular atrophy: clinical and molecular study of a large family

This is the first report SBMA from Turkey and clinical findings were confirmed with molecular genetic diagnosis and patients with SBMA have expansion of CAG trinucleotid repeats in the androgen receptor (AR) gene.

No association between the androgen receptor gene CAG repeat and impaired sperm production in Swedish men

To assess a possible influence of the polymorphic CAG repeat in the A R gene on sperm production in the population, genotyped 294 healthy unselected Swedish males and 33 Swedish men with at least one year's infertility together with abnormal sperm samples, and compared the distribution of alleles containing different numbers of CAG between the two groups.

X‐Linked recessive bulbospinal neuronopathy: Clinical phenotypes and cag repeat size in androgen receptor gene

Clinical phenotypes and the CAG repeat size of the androgen receptor gene were assessed in 95 Japanese patients with X‐linked recessive bulbospinal neuronopathy and extensive variation in phenotypic severity in patients with the same size of C AG repeat was present even among the siblings, suggesting that other factors than CAGrepeat size influence the phenotypes.



Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism.

A moderate-frequency HindIII RFLP has been found which should be useful in genetic linkage analysis of the various inherited forms of androgen insensitivity.

Localization of the gene for X‐linked spinal muscular atrophy

This analysis localizes the gene defect for this form of anterior horn cell disease and finds significant linkage to the marker DXYS1 on the proximal X chromosome long arm and loose linkage or nonlinkage to markers elsewhere.

X-linked recessive bulbospinal neuronopathy: a report of ten cases.

A form of adult onset 'bulbospinal muscular atrophy' of X-linked recessive inheritance is described in 10 patients from eight families and the importance of recognising this distinctive disorder in single cases is emphasised.

The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate.

Cl cloning of the complete coding sequence of the human androgen receptor (hAR) reveals identical sequences in the DNA- and hormone-binding domains, with an overall homology of 85%.

The rat androgen receptor: primary structure, autoregulation of its messenger ribonucleic acid, and immunocytochemical localization of the receptor protein.

A 15 amino acid peptide with sequence derived from the deduced androgen receptor sequence was synthesized and used as immunogen in raising receptor antibodies in rabbits and reacted with high titer against the synthetic peptide by enzyme-linked immunosorbent assay and against the native [3H]dihydrotestosterone-labeled androgens receptor as evidenced by an increase in receptor sedimentation rate determined by sucrose gradient centrifugation.

Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies.

  • J. Ott
  • Biology
    American journal of human genetics
  • 1974
Likelihood methods can be shown to extract all possible information from the phenotypes in pedigrees, and laborious calculations have been undertaken by Morton in his investigation on the linkage between elliptocytosis and Rh.

Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing.

Direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past.

Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats

  • Wh Yu
  • Biology, Medicine
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1989
Results indicated that TP treatment significantly attenuated neuronal loss in prepubertal and young adult female rats in a dose- and time-dependent manner.