KEGG DISEASE: Spinal muscular atrophy

DISEASE: Spinal muscular atrophy

Entry

H00455                      Disease

Name

Spinal muscular atrophy

Subgroup

Werdning-Hoffman disease (SMA1)
Spinal muscular atrophy type II (SMA2)
Kugeleberg-Welander disease (SMA3)
Spinal muscular atrophy type IV (SMA4)
X-linked SMA (SMAX)
SMA proximal adult autosomal dominant (SMAPAD)
SMA, lower extremity-predominant, autosomal dominant (SMALED)
Spinal muscular atrophy, infantile, James type (SMAJI)

Description

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscle atrophy and paralysis. The most common form of SMA is caused by mutations of the SMN gene, that encodes the SMN protein, which regulates snRNP assembly. Four types of SMA are recognized depending on the age of onset and the severity of the disease: type I (Werdning-Hoffman), type II (intermediate), type III (Kugeleberg-Welander) and type IV (adult form). Other forms of spinal muscular atrophy are caused by mutation of other genes, some known and others not yet defined.

Category

Neurodegenerative disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
  Motor neuron diseases or related disorders
   8B61  Spinal muscular atrophy
    H00455  Spinal muscular atrophy
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H00455  Spinal muscular atrophy

Network

nt06515 Regulation of kinetochore-microtubule interactions

Gene

(SMA1,2,3,4) SMN1 [HSA:6606] [KO:K13129]
(SMA3) SMN2 [HSA:6607] [KO:K13129]
(SMAX1) AR [HSA:367] [KO:K08557]
(SMAX2) UBA1 [HSA:7317] [KO:K03178]
(SMAX3) ATP7A [HSA:538] [KO:K17686]
(SMAPAD) VAPB [HSA:9217] [KO:K10707]
(SMALED1) DYNC1H1 [HSA:1778] [KO:K10413]
(SMALED2) BICD2 [HSA:23299] [KO:K18739]
(SMAJI) GARS1 [HSA:2617] [KO:K01880]

Drug

Nusinersen sodium [DR:D10791]
Onasemnogene abeparvovec [DR:D11559] (bi-allelic SMN1 mutations)
Risdiplam [DR:D11406]

Comment

See H00062 for detail of SMAX1.
See also H00856 Distal hereditary motor neuropathies (dHMN).

Other DBs

ICD-11:

8B61

ICD-10:

G12.0 G12.1

MeSH:

D009134

OMIM:

253300 253550 253400 271150 313200 301830 300489 182980 158600 615290 619042

Reference

PMID:20302191

Authors

Stavarachi M, Apostol P, Toma M, Cimponeriu D, Gavrila L

Title

Spinal muscular atrophy disease: a literature review for therapeutic strategies.

Journal

J Med Life 3:3-9 (2010)

Reference

PMID:12872254 (SMN1)

Authors

Cusco I, Lopez E, Soler-Botija C, Jesus Barcelo M, Baiget M, Tizzano EF

Title

A genetic and phenotypic analysis in Spanish spinal muscular atrophy patients with c.399_402del AGAG, the most frequently found subtle mutation in the SMN1 gene.

Journal

Hum Mutat 22:136-43 (2003)
DOI:10.1002/humu.10245

Reference

PMID:19716110 (SMN2)

Authors

Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AH, Kissel JT

Title

A positive modifier of spinal muscular atrophy in the SMN2 gene.

Journal

Am J Hum Genet 85:408-13 (2009)
DOI:10.1016/j.ajhg.2009.08.002

Reference

PMID:2062380 (AR)

Authors

La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH

Title

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

Journal

Nature 352:77-9 (1991)
DOI:10.1038/352077a0

Reference

PMID:18179898 (UBA1)

Authors

Ramser J, Ahearn ME, Lenski C, Yariz KO, Hellebrand H, von Rhein M, Clark RD, Schmutzler RK, Lichtner P, Hoffman EP, Meindl A, Baumbach-Reardon L

Title

Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy.

Journal

Am J Hum Genet 82:188-93 (2008)
DOI:10.1016/j.ajhg.2007.09.009

Reference

PMID:20170900 (ATP7A)

Authors

Kennerson ML, Nicholson GA, Kaler SG, Kowalski B, Mercer JF, Tang J, Llanos RM, Chu S, Takata RI, Speck-Martins CE, Baets J, Almeida-Souza L, Fischer D, Timmerman V, Taylor PE, Scherer SS, Ferguson TA, Bird TD, De Jonghe P, Feely SM, Shy ME, Garbern JY

Title

Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy.

Journal

Am J Hum Genet 86:343-52 (2010)
DOI:10.1016/j.ajhg.2010.01.027

Reference

PMID:15372378 (VAPB)

Authors

Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, Webb J, Skehel P, Zatz M

Title

A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.

Journal

Am J Hum Genet 75:822-31 (2004)
DOI:10.1086/425287

Reference

PMID:22459677 (DYNC1H1)

Authors

Harms MB, Ori-McKenney KM, Scoto M, Tuck EP, Bell S, Ma D, Masi S, Allred P, Al-Lozi M, Reilly MM, Miller LJ, Jani-Acsadi A, Pestronk A, Shy ME, Muntoni F, Vallee RB, Baloh RH

Title

Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.

Journal

Neurology 78:1714-20 (2012)
DOI:10.1212/WNL.0b013e3182556c05

Reference

PMID:23664116 (BICD2)

Authors

Neveling K, Martinez-Carrera LA, Holker I, Heister A, Verrips A, Hosseini-Barkooie SM, Gilissen C, Vermeer S, Pennings M, Meijer R, te Riele M, Frijns CJ, Suchowersky O, MacLaren L, Rudnik-Schoneborn S, Sinke RJ, Zerres K, Lowry RB, Lemmink HH, Garbes L, Veltman JA, Schelhaas HJ, Scheffer H, Wirth B

Title

Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy.

Journal

Am J Hum Genet 92:946-54 (2013)
DOI:10.1016/j.ajhg.2013.04.011

Reference

PMID:32181591 (GARS1)

Authors

Markovitz R, Ghosh R, Kuo ME, Hong W, Lim J, Bernes S, Manberg S, Crosby K, Tanpaiboon P, Bharucha-Goebel D, Bonnemann C, Mohila CA, Mizerik E, Woodbury S, Bi W, Lotze T, Antonellis A, Xiao R, Potocki L

Title

GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment.

Journal

Am J Med Genet A 182:1167-1176 (2020)
DOI:10.1002/ajmg.a.61544

» Japanese version

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Disease (11)   
   OMIM (11)   
Drug (4)   
   KEGG DRUG (4)   
Gene (17)   
   KEGG ORTHOLOGY (8)   
   KEGG GENES (9)   
Literature (10)   
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