Connexion

GENATLAS PHENOTYPE

last update : 11-05-2018

Symbol	SBMA
Location	Xq12
HGNC id	10543
Name	spinal and bulbar muscular atrophy
Other name(s)	Kennedy disease Kennedy spinal and bulbar muscular atrophy
Corresponding gene	AR
Other symbol(s)	KD, SMAX1
Main clinical features	adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor muscle weakness and atrophy, fasciculations, dysphagia and dysarthia associated with gynecomastia and testicular atrophy and mild androgen insensitivity maybe due to poor and weak interaction of RAN (ARA24) with longer poly-Q repeat (see RAN)
Genetic determination	sex linked
Function/system disorder	neuromuscular
Type	disease

Gene product

Name

androgen receptor (AR)

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

repeat expansion		other	triplet (CAG) repeat amplification (polyglutamine stretch, 38-62) accumulating in both cytoplasmic and nuclear aggregates with a prominent somatic mosaicism observed in the cardiac and skeletal muscle

Remark(s)

mitochondrial dysfunction in SBMA cell and animal models, either through indirect effects on the transcription of nuclear-encoded mitochondrial genes or through direct effects of the mutant protein on mitochondria or both (Ranganathan 2009)

Genotype/Phenotype correlations

longer CAG repeat is more closely linked to the motor-dominant phenotype and a shorter CAG repeat is more closely linked to the sensory-dominant phenotype, and CAG repeat size differentially correlates with motor- and sensory-dominant phenotypes (Suzuki 2008)