SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings

Journal of Neurology

Volumn 253, Issue 1, 2006, Pages 21-25

  Cusco I ^a   Barcelo M J ^a   Rojas Garcia R ^b   Illa, I ^b   Gamez J ^c   Cervera, C ^c   Pou, A ^d   Izquierdo, G ^e   Baiget, M ^a   Tizzano, E F ^a  

^a HOSPITAL DE LA SANTA CREU I SANT PAU   (Spain)

^b Sant Pau University Hospital   (Spain)

^c HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^d HOSPITAL DEL MAR   (Spain)

^e HOSPITAL UNIVERSITARIO VIRGEN MACARENA   (Spain)

Author keywords

Discordant phenotype; Modifier genes; Siblings; SMN2 copy number; Spinal muscular atrophy

Indexed keywords

SURVIVAL MOTOR NEURON PROTEIN; SURVIVAL MOTOR NEURON PROTEIN 2; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CLINICAL ARTICLE; DISEASE SEVERITY; FEMALE; GENE LOCUS; GENE MUTATION; GENETIC MARKER; GENETIC VARIABILITY; HEREDITY; HUMAN; MALE; PATHOGENESIS; PHENOTYPIC VARIATION; PRIORITY JOURNAL; SIBLING; SPINAL MUSCULAR ATROPHY;

ADULT; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; FAMILY HEALTH; FEMALE; GENE DOSAGE; HUMANS; MALE; MIDDLE AGED; MUSCULAR ATROPHY, SPINAL; NERVE TISSUE PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; RNA-BINDING PROTEINS;

EID: 31544446845     PISSN: 03405354     EISSN: 14321459     Source Type: Journal    
DOI: 10.1007/s00415-005-0912-y     Document Type: Article

References (18)

1. Andreassi C, Angelozzi C, Tiziano FD, Vitali T, De Vincenzi E, Boninsegna A, Villanova M, Bertini E, Pini A, Neri G, Brahe C (2004) Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy. Eur J Hum Genet 12:59-65
2. Bouwsma G, Leschot NJ (1986) Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis. Clin Genet 30:145-149
3. Brichta L, Hofmann Y, Hahnen E, Siebzehnrubl FA, Raschke H, Blumcke I, Eyupoglu IY, Wirth B (2003) Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet 12:2481-2489
4. Bussaglia E, Tizzano EF, Illa I, Cervera C, Baiget M (1997) Cramps and minimal EMG abnormalities as preclinical manifestations of spinal muscular atrophy patients with homozygous deletions of the SMN gene. Neurology 48:1443-1445
5. Capon F, Levato C, Merlini L, Angelini C, Mostacciuolo ML, Politano L, Novelli G, Dallapiccola B (1996) Discordant clinical outcome in type III spinal muscular atrophy sibships showing the same deletion pattern. Neuromuscul Disord 6:261-264
6. Cobben JM, van der Steege G, Grootscholten P, et al. (1995) Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy. Am J Hum Genet 57:805-808
7. Cusco I, Barceló MJ, Baiget M, Tizzano E (2002) Implementation of SMA carrier testing in genetic laboratories: Comparison of two methods for quantifying the SMN1 gene. Hum Mutat 20:452-459
8. Cusco I, Lopez E, Soler-Botija C, Barcelo MJ, Baiget M, Tizzano EF (2003) A genetic and phenotypic analysis in Spanish spinal muscular atrophy patients with c 0.399_402del AGAG, the most frequently found subtle mutation in the SMN1 gene. Hum Mutat 22:136-143
9. Emery AE (1971) The nosology of spinal muscular atrophies. J Med Genet 8:481-495
10. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B (2002) Quantitative Analyses of SMN1 and SMN2 Based on Real-Time LightCycler PCR: Fast and Highly Reliable carrier testing and Prediction of severity of Spinal Muscular Atrophy. Am J Hum Genet 70:358-368
11. Gomez R (1994) The clinical examination in Myology. In: Engel AG, Franzini-Armstrong C (eds) 2nd edition Mc Graw-Hill, New York 1:746-763
12. Hahnen E, Forkert R, Marke C, et al. (1995) Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals. Hum Mol Genet 10:1927-1933
13. Harada Y, Sutomo R, Sadewa AH, Akutsu T, Takeshima Y, Wada H, Matsuo M, Nishio H (2002) Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity. J Neurol 249:1211-1219
14. Helmken C, Hofmann Y, Schoenen F, Oprea G, Raschke H, Rudnik-Schoneborn S, Zerres K, Wirth B (2003) Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1. Hum Genet 114:11-21
15. Lefebvre S, Bürglen L, Beboullet S, et al. (1995) Identification and characterisation of a spinal muscular atrophy-determining gene. Cell 80:155-165
16. nd ed. London, UK: Royal Society of Medicine Press, pp 37-41
17. Roy N, Mahadevan MS, Mclean M, et al. (1995) The gene for neural apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80:167-178
18. T) gene deletions in asymptomatic carriers of spinal muscular atrophy. Hum Mol Genet 5:359-365