SBMA AR

Disease ID
SBMA
Gene ID
AR
Updated
Feb 5, 2025
v2.2.1

Disease

Name
Spinal and bulbar muscular atrophy, Kennedy Disease
Inheritance
X-linked recessive
Description
Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare X-linked recessive motor neuron disease characterized by proximal and bulbar muscle wasting1 .
Prevalence
1 30,000
1-2/100,000 (population-specific, higher in Finnish population, Canadian population)2 ; 1/30,0003 ; mutation frequency of 1:3182 10x more frequent than reported disease prevalence of 1 in 30,0004 . Only documented in patients with European/Asian ancestry, including Scandinavian, English, Belgian, French, Italian, German, Polish, Spanish, Swiss, Moroccan, Turkish, Chinese, Japanese (more common because of a founder effect), Korean, and Vietnamese populations5 .
Age of Onset(Typical)Years8  8320  49
Age of Onset Details
Typical: 20-496 , Range: 87 - 838 .

Locus

Details
Intermediate alleles indicate reduced penetrance5 . Expansions larger than the pathogenic threshold in the AR gene should be evaluated carefully. Interruptions have not been observed in patient cases; it has been proposed that longer alleles with interruptions may not be pathogenic9 . Non-canonical motif CAA observed10 . Expansions are also detected ten-fold more often in a general population than would be expected by disease prevalence4 . Clinical evaluation and phenotypic matching may be necessary to determine diagnosis even in the presence of a pure expanded allele. It has been proposed that contractions may play a role in disease11 . Disease may be subclinical in females12 , and can be clinically heterogeneous even within the same family13 .
Mechanism
GoF
Polyglutamine alters protein conformation leading to gain-of-function neurodegeneration14,15 . Transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction also play causative roles in the neurodegeneration16 .
Year
199117 ; the first triplet disease to be discovered18
Location in Gene
Exon 1
Gene Strand

Alleles

Ref. Motif
GCA
Pathogenic (ref.)
GCA
Pathogenic (gene)
AGC
BenignIntermediatePathogenicUnits9  3436  3738  68

gnomAD

References

Direct supporting references for info on this page.

1
Ontology Lookup Service (OLS)
mondo:0010735
2
Advancing Epidemiology and Genetic Approaches for the Treatment of Spinal and Bulbar Muscular Atrophy: Focus on Prevalence in the Indigenous Population of Western Canada.
Harry,Wilton-Clark, Ammar,Al-Aghbari, Jessica,Yang, Toshifumi,Yokota
Genes · 2023-08-17
pmid:37628685
3
Orphanet: Kennedy disease
orphanet:481
4
Unexpected frequency of the pathogenic AR CAG repeat expansion in the general population.
Matteo,Zanovello, Kristina,Ibáñez, Anna-Leigh,Brown, Prasanth,Sivakumar, Alessandro,Bombaci, Liana,Santos, Joke J F A,van Vugt, Giuseppe,Narzisi, Ramita,Karra, Sonja W,Scholz, Jinhui,Ding, J Raphael,Gibbs, Adriano,Chiò, Clifton,Dalgard, Ben,Weisburd, Michael G,Hanna, Linda,Greensmith, Hemali,Phatnani, Jan H,Veldink, Bryan J,Traynor, James,Polke, Henry,Houlden, Pietro,Fratta, Arianna,Tucci
Brain : a journal of neurology · 2023-07-03
pmid:36797998
5
Spinal and Bulbar Muscular Atrophy
Albert,La Spada
GeneReviews® · 1993-01-01
genereviews:NBK1333
6
Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world.
A,Lund, B,Udd, V,Juvonen, P M,Andersen, K,Cederquist, M,Davis, C,Gellera, C,Kölmel, L O,Ronnevi, A D,Sperfeld, S A,Sörensen, L,Tranebjaerg, L,Van Maldergem, M,Watanabe, M,Weber, L,Yeung, M L,Savontaus
European journal of human genetics : EJHG · 2001-06-01
pmid:11436124
7
A family with early-onset and rapidly progressive X-linked spinal and bulbar muscular atrophy.
A,Echaniz-Laguna, E,Rousso, M,Anheim, M,Cossée, C,Tranchant
Neurology · 2005-04-26
pmid:15851746
8
A Case of Very Late Onset Spinobulbar Muscular Atrophy with Normal Creatine Kinase
Joseph,Conway, Yuebing,Li, Sakhi,Bhansali
RRNMF Neuromuscular Journal · 2024-12-17
doi:10.17161/2tmg0f25
9
Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions.
Pietro,Fratta, Toby,Collins, Sally,Pemble, Suran,Nethisinghe, Anny,Devoy, Paola,Giunti, Mary G,Sweeney, Michael G,Hanna, Elizabeth M C,Fisher
Neurobiology of aging · 2013-09-13
pmid:24041967
10
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.
Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson
Science advances · 2022-03-04
pmid:35245110
11
CAG repeat contraction in the androgen receptor gene in three brothers with mental retardation.
R F,Kooy, E,Reyniers, K,Storm, L,Vits, D,van Velzen, P E,de Ruiter, A O,Brinkmann, A,de Paepe, P J,Willems
American journal of medical genetics · 1999-07-30
pmid:10398229
12
Kennedy disease in two sisters with biallelic CAG expansions of the androgen receptor gene.
Kai Ivar,Müller, Øivind,Nilssen, Maria,Nebuchenykh, Sissel,Løseth, Christoffer,Jonsrud, Gry,Hoem, Marijke,Van Ghelue, Kjell Arne,Arntzen
Neuromuscular disorders : NMD · 2021-11-19
pmid:34922802
13
Phenotypic differences in a large family with Kennedy's disease from the Middle Black Sea region of Turkey.
Hatice,Karaer, Yüksel,Kaplan, Semiha,Kurt, Asli,Gundogdu, Begüm,Erdoğan, Nazli A,Başak
Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases · 2010-01-01
pmid:20184516
14
Tandem repeats mediating genetic plasticity in health and disease.
Anthony J,Hannan
Nature reviews. Genetics · 2018-02-05
pmid:29398703
15
Clinical and neuroimaging review of triplet repeat diseases.
Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe
Japanese journal of radiology · 2022-09-28
pmid:36169768
16
Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).
Masahisa,Katsuno, Fumiaki,Tanaka, Hiroaki,Adachi, Haruhiko,Banno, Keisuke,Suzuki, Hirohisa,Watanabe, Gen,Sobue
Progress in neurobiology · 2012-05-15
pmid:22609045
17
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.
A R,La Spada, E M,Wilson, D B,Lubahn, A E,Harding, K H,Fischbeck
Nature · 1991-07-04
pmid:2062380
18
Bulbospinal muscular atrophy: Kennedy's disease.
Michael,Sinnreich, Christopher Jon,Klein
Archives of neurology · 2004-08-01
pmid:15313856

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)