KEGG   DISEASE: Spinal muscular atrophy
H00455                      Disease                                
Spinal muscular atrophy
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)
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.
Neurodegenerative disease
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
nt06515 Regulation of kinetochore-microtubule interactions
(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]
Nusinersen sodium [DR:D10791]
Onasemnogene abeparvovec [DR:D11559] (bi-allelic SMN1 mutations)
Risdiplam [DR:D11406]
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
Stavarachi M, Apostol P, Toma M, Cimponeriu D, Gavrila L
Spinal muscular atrophy disease: a literature review for therapeutic strategies.
J Med Life 3:3-9 (2010)
PMID:12872254 (SMN1)
Cusco I, Lopez E, Soler-Botija C, Jesus Barcelo M, Baiget M, Tizzano EF
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.
Hum Mutat 22:136-43 (2003)
PMID:19716110 (SMN2)
Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AH, Kissel JT
A positive modifier of spinal muscular atrophy in the SMN2 gene.
Am J Hum Genet 85:408-13 (2009)
PMID:2062380 (AR)
La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.
Nature 352:77-9 (1991)
PMID:18179898 (UBA1)
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
Rare missense and synonymous variants in UBE1 are associated with X-linked infantile spinal muscular atrophy.
Am J Hum Genet 82:188-93 (2008)
PMID:20170900 (ATP7A)
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
Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy.
Am J Hum Genet 86:343-52 (2010)
PMID:15372378 (VAPB)
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
A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.
Am J Hum Genet 75:822-31 (2004)
PMID:22459677 (DYNC1H1)
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
Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.
Neurology 78:1714-20 (2012)
PMID:23664116 (BICD2)
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
Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy.
Am J Hum Genet 92:946-54 (2013)
PMID:32181591 (GARS1)
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
GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment.
Am J Med Genet A 182:1167-1176 (2020)

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