CAG repeat contraction in the androgen receptor gene in three brothers with mental retardation

Kooy, R. Frank; Reyniers, Edwin; Storm, Katrien; Vits, Lieve; Velzen, D. van; Ruiter, Petra E. de; Brinkmann, Albert O.; Paepe, Anne De; Willems, Patrick J.

doi:10.1002/(sici)1096-8628(19990730)85:3<209::aid-ajmg4>3.0.co;2-2

Cited by 11 publications

References 22 publications

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Clinical study and haplotype analysis in two brothers with Partington syndrome

Frints¹,

Borghgraef²,

Froyen³

et al. 2002

Am. J. Med. Genet.

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Partington et al. [1988] described a three-generation family (MRXS1, MIM *309510, PRTS) with a syndromic form of X-linked mental retardation (XLMR). The clinical features in 10 affected males included mild to moderate MR, dystonic movements of the hands, and dysarthria. After refinement, the PRTS locus was mapped to marker DXS989 (with maximum LOD score of 3.1) with flanking markers DXS365 and DXS28. Since then, no other patients with a similar phenotype have been described. We present a detailed description of the neurological symptoms and the disease history of two brothers with the clinical features of PRTS. Psychomotor development was delayed in both, and neurological features included mild to moderate mental retardation, dysarthria, facial muscle weakness, severe dysdiadochokinesis, slow dystonic movements, and mild spasticity of the hands, without ataxia or spasticity of the legs. The symptoms were nonprogressive and extrapyramidal, and without cerebellar involvement. In general, behavior of the two brothers was friendly and quiet, although the elder brother had periods of depressed mood and outbursts of anger. Karyotypes and subsequent investigation of the subtelomeres as well as DNA analysis of the FMR1 gene, the androgen receptor gene, and the DM locus did not reveal a genetic abnormality. Haplotype analysis showed that the affected brothers share the PRTS region at Xp22.1. Mutation screening of the PDH-E1alpha gene did not reveal a pathogenic mutation.

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Clinical study and haplotype analysis in two brothers with Partington syndrome

Frints¹,

Borghgraef²,

Froyen³

et al. 2002

Am. J. Med. Genet.

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Kennedy’s disease (spinal and bulbar muscular atrophy): a clinically oriented review of a rare disease

Breza

Koutsis

2018

J Neurol

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Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a rare, X-linked hereditary lower motor neuron disease, characterized by progressive muscular weakness. An expanded trinucleotide repeat (CAG > 37) in the androgen receptor gene (AR), encoding glutamine, is the mutation responsible for Kennedy's disease. Toxicity of this mutant protein affects both motor neurons and muscles. In this review, we provide a comprehensive, clinically oriented overview of the current literature regarding Kennedy's disease, highlighting gaps in our knowledge that remain to be addressed in further research. Kennedy's disease mimics are also discussed, as are ongoing and recently completed therapeutic endeavours.

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Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease)

Finsterer

Sorarù

2015

J Mol Neurosci

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Spinal and bulbar muscular atrophy (SBMA) is regarded as a disorder with adult onset between third and fifth decade of life. However, there is increasing evidence that SBMA may start already before adulthood. The present study investigated the following: (1) Which clinical manifestations have been described so far in the literature as initial manifestations? (2) Which was the age at onset of these manifestations? and (3) Is age at onset dependent on the CAG-repeat length if non-motor manifestations are additionally considered? Data for this review were identified by searches of MEDLINE using appropriate search terms. Onset manifestations in SBMA can be classified as frequent, rare, motor, non-motor, or questionable. Frequent are muscle weakness, cramps, fasciculations/twitching, tremor, dysarthria, dysphagia, or gynecomastia. Rare are myalgia, easy fatigability, exercise intolerance, polyneuropathy, hyper-CKemia, under-masculinized genitalia, scrotal hypospadias, microphallus, laryngospasm, or oligospermia. Questionable manifestations include sensory disturbances, cognitive impairment, increased pituitary volume, diabetes, reduced tongue pressure, elevated creatine-kinase, or low androgens/high estrogens. Age at onset is highly variable ranging from 4-76 years. Non-motor manifestations develop usually before motor manifestations. Age at onset depends on what is considered as an onset manifestation. Considering non-motor onset manifestations, age at onset is independent of the CAG-repeat size. In conclusion, age at onset of SBMA depends on what is regarded as onset manifestation. If non-motor manifestations are additionally considered, age at onset is independent of the CAG-repeat length. Since life expectancy is hardly reduced in SBMA, re-investigation of patients from published studies with regard to their initial disease profiles is recommended.

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CAG repeat contraction in the androgen receptor gene in three brothers with mental retardation

Cited by 11 publications

References 22 publications

Clinical study and haplotype analysis in two brothers with Partington syndrome

Clinical study and haplotype analysis in two brothers with Partington syndrome

Kennedy’s disease (spinal and bulbar muscular atrophy): a clinically oriented review of a rare disease

Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease)

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