Spinal muscular atrophy: molecular genetics and diagnostics

References

• Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA). Hum. Genet. 111(6), 477–500 (2002).
   PubMed Web of Science ®Google Scholar
• •• First comprehensive review demonstrating how to calculate genetic risks in various spinal muscular atrophy (SMA) clinical settings.
   Google Scholar
• Munsat TL, Davies KE. International SMA consortium meeting. Neuromuscul
   Google Scholar
• (5–6), 423–428 (1992).
   Google Scholar
• Zerres K, Davies KE. 59th ENMC International Workshop: spinal muscular atrophies: recent progress and revised diagnostic criteria 17–19 April 1998, Soestduinen, The Netherlands. Neummuscul Disonl 9(4), 272–278 (1999).
   Google Scholar
• Rudnik-Schonebom S, Goebel HH, Schlote W etal Classical infantile spinal muscular atrophy with SMN deficiency causes sensory neuronopathy. Neumlogy 60(6), 983–987 (2003).
   PubMed Web of Science ®Google Scholar
• Zerres K, Rudnik-Schonebom S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch. Neural. 52(5), 518–523 (1995).
   Google Scholar
• Ogino S, Leonard DG, Rennert H, Ewens WJ, Wilson RB. Genetic risk assessment in carrier testing for spinal muscular atrophy. Am. j Med. Genet. 110(4), 301–307 (2002).
   Google Scholar
• Brahe C, Servidei S, Zappata S etal Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy. Lancet 346 (8977), 741–742 (1995).
   PubMed Web of Science ®Google Scholar
• Zerres K, Rudnik-Schonebom S, Forkert R, Wirth B. Genetic basis of adult-onset spinal muscular atrophy. Lancet 346(8983), 1162 (1995).
   PubMed Web of Science ®Google Scholar
• Zerres K, Wirth B, Rudnik-Schoenebom S. Spinal muscular atrophy — clinical and genetic correlation. Neuromuscul Disonl 7, 202–207 (1997). toRudnik-Schonebom S, Forkert R, Hahnen E, Wirth B, Zerres K. Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings. Neumpediatrics27(1), 8–15 (1996). degeneration associated with deletion of the SM/VTgene. Neurology 49(3), 848–851 (1997).
   Web of Science ®Google Scholar
• Rudnik-Schoneborn S, Forkert R, Hahnen E, Wirth B, Zerres K. Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings. Neuropediatrics 27(1), 8–15 (1996).
   PubMed Web of Science ®Google Scholar
• Goldberg MJ. Syndrome of orthopaedic importance. In: Lovell and Winter’s Pediatric Orthopaedics. Morrissy RT, Weinstein SL (Eds), Lippincott-Raven Publishers, PA, USA, 262–271 (1996).
   Google Scholar
• Gordon N. Arthrogryposis multiplex congenita. Brain Dev. 20(7), 507–511 (1998).
   Google Scholar
• Talbot K, Davies KE. Spinal muscular atrophy. Semin. Neurol. 21(2), 189–197(2001).
   PubMed Web of Science ®Google Scholar
• Burglen L, Amiel J, Viollet L et al. Survival motor neurone gene deletion in the arthrogryposis multiplex congenita–spinal muscular atrophy association. J. Clin. Invest. 98(5), 1130–1132 (1996).
   Google Scholar
• Bingham PM, Shen N, Rennert H et al. Arthrogryposis due to infantile neuronal degeneration associated with deletion of the SMNT gene. Neurology 49(3), 848–851 (1997).
   PubMed Web of Science ®Google Scholar
• Ogino S, Leonard DG, Rennert H, Wilson RB. Spinal muscular atrophy genetic testing experience at an academic medical center. .1. Mal Diagn. 4(1), 53–58 (2002).
   Google Scholar
• Poets C, Heyer R, von der Hardt H, Walter GE Acute respiratory insufficiency as the initial clinical manifestations of spinal muscular atrophy. Monatsschr I6Pderheilkd 138(3), 157–159 (1990).
   Google Scholar
• Sivan Y, Galvis A. Early diaphragmatic paralysis in infants with genetic disorders. Clin. Pecliatr 29(3), 169–171 (1990).
   PubMed Web of Science ®Google Scholar
• Mellins RB, Hays AP, Gold AP, Berdon WE, Bowdler JD. Respiratory distress as the initial manifestation of Werdnig—Hoffmann disease. Pecliatrics53(1), 33–40 (1974).
   PubMed Web of Science ®Google Scholar
• McWilliam RC, Gardner—Medwin D, Doyle D, Stephenson JB. Diaphragmatic paralysis due to spinal muscular atrophy. An unrecognised cause of respiratory failure in infancy? Arch. Dis. Child. 60(2), 145–149 (1985).
   Google Scholar
• Lefebvre S, Burglen L, Reboullet S etal Identification and characterization of a spinal muscular atrophy-determining gene. Ce1180(1), 155–165 (1995).
   Google Scholar
• ••Describes the identification of the diseasegene for SMA. A complete contig of the disease gene region on chromosome 5 is provided.
   Google Scholar
• Burglen L, Lefebvre S, Clermont 0 eta]. Structure and organization of the human survival motor neurone (SMA) gene. Genomics 32 (3), 479–482 (1996) .
   Google Scholar
• McAndrew PE, Parsons DW, Simard LR eta]. Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. Am. J. Hum. Genet. 60(6), 1411–1422 (1997).
   Google Scholar
• ••Describes the first robust method toquantify the copy numbers of SMN/ and SMN2using competitive quantitative PCR
   Google Scholar
• Gerard B, Ginet N, Matthijs G etal. Genotype determination at the survival motor neurone locus in a normal population and SMA carriers using competitive PCR and primer extension. Hum. Mutat. 16(3), 253–263 (2000).
   Google Scholar
• Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl Acad. Sc 96,6307–6311 (1999).
   PubMed Web of Science ®Google Scholar
• •Demonstrated that the translationally silent single nucleotide polymorphism at position 840 in SMN2exon 7 is responsible for the inefficient splicing of the SMN2transcript.
   Google Scholar
• Monani UR, Lorson CL, Parsons DW et al A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN/ from the copy gene 51V1N2 Hum. Mal Genet. 8(7), 1177–1183 (1999).
   Google Scholar
• •Demonstrated that the translationally silent single nucleotide polymorphism at position 840 in SMN2 exon7 is responsible for the inefficient splicing of the SMN2transcript.
   Google Scholar
• Kashima T, Manley JL. A negative element in SM/V2exon 7 inhibits splicing in spinal muscular atrophy. Nature Genet. 34(4), 460–463 (2003).
   Google Scholar
• •Demonstrated that the translationally silent single nucleotide polymorphism at position 840 in SMN2exon 7 activates an exonic splice silencer.
   Google Scholar
• Kerr DA, Nery JP, Traystman RJ, Chau BN, Hardwick JM. Survival motor neurone protein modulates neuron-specific apoptosis. Proc. Natl Acad. Sc]. USA 97(24), 13312–13317 (2000).
   Google Scholar
• Frugier T, Nicole S, Cifuentes-Diaz C, Melki J. The molecular bases of spinal muscular atrophy. CUI7: Opin. Genet. Dev.12(3), 294–298 (2002).
   Google Scholar
• •Excellent overview of SMA.
   Google Scholar
• Paushkin S, Gubitz AK, Massenet S, Dreyfuss G. The SMN complex, an assemblyosome of ribonucleoproteins. Cum Opin. Cell Biol. 14(3), 305–312 (2002).
   Google Scholar
• •Excellent review of the function of SMN.
   Google Scholar
• Meister G, Eggert C, Fischer U. SMN-mediated assembly of RNPs: a complex story. 7iends Cell Biol. 12(10), 472–478 (2002).
   Google Scholar
• •Excellent review of the function of SMN.
   Google Scholar
• Wirth B. An update of the mutation spectrum of the survival motor neurone gene (SMVVin autosomal recessive spinal muscular atrophy (SMA). Hum. Mutat. 15(3), 228–237 (2000).
   PubMed Web of Science ®Google Scholar
• •First comprehensive review of SMNI mutations.
   Google Scholar
• Wirth B, Hahnen E, Morgan K etal Allelic association and deletions in autosomal recessive proximal spinal muscular atrophy: association of marker genotype with disease severity and candidate cDNAs. Hum Mal Genet. 4(8), 1273–1284 (1995).
   Google Scholar
• Burlet P, Burglen L, Clermont 0 et al Large scale deletions of the 5q13 region are specific to Werdnig—Hoffmann disease. Merl Genet. 33(4), 281–283 (1996).
   Google Scholar
• Simard LR, Rochette C, Semionov A, Morgan K, Vanasse M. SM/V(77 and NAIP mutations in Canadian families with spinal muscular atrophy (SMA): genotype/phenotype correlations with disease severity. Am. j Med. Genet. 72(1), 51–58 (1997).
   Google Scholar
• Burghes AH. When is a deletion not a deletion? When it is converted. Am. Hum. Genet. 61(1), 9–15 (1997).
   Google Scholar
• Hahnen E, Schonling J, Rudnik- Schonebom S, Zerres K, Wirth B. Hybrid survival motor neurone genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease. Am. J. Hum. Genet. 59(5), 1057–1065 (1996).
   Google Scholar
• Cusco I, Barcelo MJ, del Rio E etal Characterisation of SM/Vhybrid genes in Spanish SMA patients: de novo, homozygous and compound heterozygous cases. Hum. Genet. 108(3), 222–229 (2001).
   PubMed Web of Science ®Google Scholar
• Campbell L, Potter A, Ignatius J, Dubowitz V, Davies K. Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am. J. Hum. Genet. 61(1), 40–50 (1997).
   Google Scholar
• Wirth B, Herz M, Wetter A etal Quantitative analysis of survival motor neurone copies: identification of subtle SMNI mutations in patients with spinal muscular atrophy, genotype—phenotype correlation and implications for genetic counseling. Am. J. Hum. Genet. 64, 1340–1356 (1999).
   PubMed Web of Science ®Google Scholar
• ••Only comprehensive study investigatingthe frequency of SMNI small intragenic mutations for each SMA type.
   Google Scholar
• Feldkotter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMNI and SM/V2based 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 (2002).
   Google Scholar
• •First description of methods to quantify the copy numbers of SMNI and SMV2 using real-time PCR
   Google Scholar
• den Dunnen JT, Antonarakis SE. Nomenclature for the description of human sequence variations. Hum. Genet. 109(1), 121–124 (2001).
   PubMed Web of Science ®Google Scholar
• den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum. Mutat. 15(1), 7–12 (2000).
   PubMed Web of Science ®Google Scholar
• Rochette CF, Surh LC, Ray PN etal Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7. Neurogenetics 1 (2), 141–147 (1997).
   Google Scholar
• Parsons DW, McAndrew PE, Monani UR etal An 11 base pair duplication in exon 6 of the SM/Vgene produces a Type I spinal muscular atrophy (SMA) phenotype: further evidence for SM/Vas the primary SMA-determining gene. Hum. Mal Genet. 5(11), 1727–1732 (1996).
   Google Scholar
• Parsons DW, McAndrew PE, Iannaccone ST etal Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect and modification of the spinal muscular atrophy phenotype by cenSMN copy number. Am. J. Hum. Genet. 63(6), 1712–1723 (1998).
   Google Scholar
• Clermont 0, Burlet P, Cruaud C etal Mutation analysis of the SM/Vgene in undeleted SMA patients. Annual meeting of the American Society of Human Genetics. Am. Hum. Genet. 61, A329 (1997).
   Google Scholar
• Martin Y, Valero A, del Castillo E, Pascual SI, Hemandez-Chico C. Genetic study of SMA patients without homozygous SMNI deletions: identification of compound heterozygotes and characterisation of novel intragenic SMNI mutations. Hum. Genet. 110(3), 257–263 (2002).
   Google Scholar
• Cusco I, Lopez E, Soler-Botija C etal A genetic and phenotypic analysis in Spanish spinal muscular atrophy patients with c.399_402de1 AGAG, the most frequently found subtle mutation in the SMV/ gene. Hum. Mutat. 22,136-143 (2003).
   Google Scholar
• Bussaglia E, Clermont 0, Tizzano E etal A frame-shift deletion in the survival motor neurone gene in Spanish spinal muscular atrophy patients. Nature Genet. 11(3), 335–337 (1995).
   Google Scholar
• Lorson CL, Strasswimmer J, Yao JM etal SMN oligomerization defect correlates with spinal muscular atrophy severity. Nature Genet. 19(1), 63–66 (1998). Expert Rev. Mot. Diagn. 4(1), (2004)
   Google Scholar
• SOSSi V, Giuli A, Vitali T etal Premature termination mutations in exon 3 of the SM/V/ gene are associated with exon skipping and a relatively mild SMA phenotype. Eur. j Hum. Genet. 9(2), 113–120 (2001).
   Google Scholar
• Stevens G, Yawitch T, Rodda J, Verhaart S, Krause A. Different molecular basis for spinal muscular atrophy in South African black patients. Am. j Med. Genet. 86(5), 420–426 (1999).
   Google Scholar
• Wilmshurst JM, Reynolds L, Van Toom R, Leisegang F, Henderson HE. Spinal muscular atrophy in black South Africans: concordance with the universal SMN/ genotype. Clin. Genet. 62(2), 165–168 (2002).
   Google Scholar
• Cusin V, Clermont 0, Gerard B, Chantereau D, Elion J. Prevalence of SM/V/ deletion and duplication in carrier and normal populations: implication for genetic counselling. J. Med. Genet. 40(4), E39 (2003).
   Google Scholar
• Wirth B, Schmidt T, Hahnen E etal De nova rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate and implications for genetic counseling. Am. J. Hum. Genet. 61(5), 1102–1111 (1997).
   Google Scholar
• ••Largest study investigating the frequencyof SMV1 de novo deletions among SMA patients lacking SMN1.
   Google Scholar
• Campbell L, Daniels RJ, Dubowitz V, Davies KE. Maternal mosaicism for a second mutational event in a Type I spinal muscular atrophy family. Am J. Hum. Genet. 63(1), 37–44 (1998).
   Google Scholar
• Chen KL, Wang YL, Rennert H etal Duplications and de nova deletions of the SM/VTgene demonstrated by fluorescence-based carrier testing for spinal muscular atrophy. Am .1. Med. Genet. 85(5), 463–469 (1999).
   Google Scholar
• Ogino S, Leonard DG, Rennert H, Gao S, Wilson RB. Heteroduplex formation in SM/Vgene dosage analysis. J. Mal Diagn. 3(4), 150–157 (2001).
   Google Scholar
• Velasco E, Valero C, Valero A, Moreno F, Hemandez-Chico C. Molecular analysis of the SM/Vand NA/Pgenes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype. Hum. Mal Genet. 5(2), 257–263 (1996).
   Google Scholar
• Roy N, Mahadevan MS, McLean M etal The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Ce1180(1), 167–178 (1995).
   Google Scholar
• Roy N, McLean MD, Besner-Johnston A etal Refined physical map of the spinal muscular atrophy gene (SMA) region at 5q13 based on YAC and cosmid contiguous arrays. Genomic526(3), 451–460 (1995).
   Google Scholar
• Rodrigues NR, Owen N, Talbot K etal Deletions in the survival motor neurone gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum. Mal Genet. 4(4), 631–634 (1995).
   Google Scholar
• Hahnen E, Forkert R, Marke C etal Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SM/Vgene in unaffected individuals. Hum. Mal Genet. 4(10), 1927–1933 (1995).
   Google Scholar
• Scharf JM, Endrizzi MG, Wetter A eta]. Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics. Nature Genet. 20(1), 83–86 (1998).
   PubMed Web of Science ®Google Scholar
• Hofmann Y, Lorson CL, Stamm S, Androphy EJ, Wirth B. Htra2-beta 1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neurone 2 (SM/V2). Proc. Natl Acad. Sci. USA 97(17), 9618–9623 (2000).
   Google Scholar
• Helmken C, Wirth B. Exclusion of Htra2-beta 1, an upregulator of full-length SM/V2transcript, as a modifying gene for spinal muscular atrophy. Hum. Genet. 107(6), 554–558 (2000).
   Google Scholar
• Helmken C, Wetter A, Rudnik-Schonebom S etal An essential SMN interacting protein (SIP1) is not involved in the phenotypic variability of spinal muscular atrophy (SMA). Eur Hum. Genet. 8(7), 493–499 (2000).
   Google Scholar
• Rochette CF, Gilbert N, Simard LR. SM/Vgene duplication and the emergence of the SM/V2gene occurred in distinct hominids: SM/V2is unique to Homo sapiens Hum. Genet. 108(3), 255–266 (2001).
   Google Scholar
• •Investigated the molecular evolution of the SMNgenes.
   Google Scholar
• Schrank B, Gotz R, Gunnersen JM etal Inactivation of the survival motor neurone gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc. Natl Acad. Sci. USA 94(18), 9920–9925 (1997).
   Google Scholar
• Monani UR, Sendtner M, Coovert DD etal The human centromeric survival motor neurone gene (SM/V4rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum. Mal Genet. 9(3), 333–339 (2000).
   Google Scholar
• •Established a mouse model of SMA.
   Google Scholar
• Monani UR, Coovert DD, Burghes AH. Animal models of spinal muscular atrophy. Hum. Mal Genet. 9(16), 2451–2457 (2000).
   Google Scholar
• Hsieh-Li HM, Chang JG, Jong YJ etal A mouse model for spinal muscular atrophy. Nature Genet. 24(1), 66–70 (2000).
   Google Scholar
• •Established a mouse model of SMA.
   Google Scholar
• Frugier T, Tiziano FD, Cifuentes-Diaz C etal Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy. Hum. Mal Genet. 9(5), 849–858 (2000).
   PubMed Web of Science ®Google Scholar
• Cifuentes-Diaz C, Frugier T, Tiziano FD etal Deletion of murine SM/Vexon 7 directed to skeletal muscle leads to severe muscular dystrophy. J. Cell Biol. 152(5), 1107–1114 (2001).
   Google Scholar
• Chan YB, Miguel-Aliaga I, Franks C etal Neuromuscular defects in a Drosophila survival motor neurone gene mutant. Hum. Mal Genet. 12(12), 1367–1376 (2003).
   PubMed Web of Science ®Google Scholar
• McWhorter ML, Monani UR, Burghes AH, Beattie CE. Knockdown of the survival motor neurone (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding. J. Cell Biol. 162(5), 919–932 (2003).
   PubMed Web of Science ®Google Scholar
• Scheffer H, Cobben JM, Matthijs G, Wirth B. Best practice guidelines for molecular analysis in spinal muscular atrophy. Eur. Hum. Genet. 9(7), 484–491 (2001).
   Google Scholar
• Melki J, Lefebvre S, Burglen L etal De nova and inherited deletions of the 5q13 region in spinal muscular atrophies. Science 264(5164), 1474–1477 (1994).
   Google Scholar
• DiDonato CJ, Morgan K, Carpten JD etal Association between Agl-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy. Am. J. Hum. Genet. 55(6), 1218–1229 (1994).
   Google Scholar
• Matthijs G, Schollen E, Legius E etal Unusual molecular findings in autosomal recessive spinal muscular atrophy. J. Med. Genet. 33(6), 469–474 (1996).
   Google Scholar
• Wang CH, Xu J, Carter TA etal Characterization of survival motor neurone (SM/VV gene deletions in asymptomatic carriers of spinal muscular atrophy. Hum. Mal Genet. 5(3), 359–365 (1996).
   PubMed Web of Science ®Google Scholar
• van der Steege G, Grootscholten P, van der Vlies P etal PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet 345,985–986 (1995).
   PubMed Web of Science ®Google Scholar
• Mailman MD, Heinz JW, Papp AC etal Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2 Genet. Med. 4(1), 20–26 (2002).
   Google Scholar
• Sutomo R, Akutsu T, Takeshima Y et al Rapid SMNI deletion test using DHPLC to screen patients with spinal muscular atrophy. Am. J. Med. Genet. 113 (2), 225–226 (2002).
   Google Scholar
• Mazzei R, Conforti FL, Muglia M etal A simple method for diagnosis of autosomal recessive spinal muscular atrophy by denaturing high-performance liquid chromatography. J. Child Neural 18(4), 269–271 (2003).
   PubMed Web of Science ®Google Scholar
• Scheffer H, Cobben JM, Mensink RG etal SMA carrier testing: validation of hemizygous SM/Vexon 7 deletion test for the identification of proximal spinal muscular atrophy carriers and patients with a single allele deletion. Eur. J. Hum. Genet. 8(2), 79–86 (2000).
   Google Scholar
• Anhuf D, Eggermann T, Rudnik-Schoneborn S, Zerres K. Determination of SMNI and SM1\2 copy number using TaqMan® technology. Hum. Mutat. 22(1), 74–78 (2003).
   Google Scholar
• •Describes methods to quantify the copy number of SMN/ and SMN2using TaqMan real-time PCR
   Google Scholar
• CUSCO II, Barcelo MJ, Baiget M, Tizzano EE Implementation of SMA carrier testing in genetic laboratories: comparison of two methods for quantifying the SMNI gene. Hum. Mutat. 20(6), 452–459 (2002).
   PubMed Web of Science ®Google Scholar
• Ogino S, Wilson RB. Quantification of PCR bias caused by a single nucleotide polymorphism in SM/Vgene dosage analysis. Mal Diagn. 4(4), 185–190 (2002).
   Google Scholar
• Parsons DW, McAndrew PE, Allinson PS etal Diagnosis of spinal muscular atrophy in an SMN non-deletion patient using a quantitative PCR screen and mutation analysis. J. Med. Genet. 35 (8), 674–676 (1998).
   Google Scholar
• Ogino S, Gao S, Leonard DG, Paessler M, Wilson RB. Inverse correlation between SMNI and SM/V2copy numbers: evidence for gene conversion from SMN2to SMIV.1. Eur. Hum. Genet. 11 (3), 275–277 (2003) Addendum in 11(9), 723.
   Google Scholar
• Van Deerlin VM, Leonard DG. Bone marrow engraftment analysis after allogeneic bone marrow transplantation. Gun. Lab. Med. 20(1), 197–225 (2000).
   Google Scholar
• Beroud C, Karliova M, Bonnefont JP eta]. Prenatal diagnosis of spinal muscular atrophy by genetic analysis of circulating fetal cells. Lancet 361(9362), 1013–1014 (2003).
   PubMed Web of Science ®Google Scholar
• Benachi A, Steffann J, Gautier E et al Fetal DNA in maternal serum: does it persist after pregnancy? Hum. Genet. 113(1), 76–79 (2003).
   Google Scholar
• Thornhill AR, Snow K. Molecular diagnostics in preimplantation genetic diagnosis. J. A/LI Diagn. 4(1), 11–29 (2002).
   PubMed Web of Science ®Google Scholar
• Verlinsky Y, Kuliev A. Preimplantation diagnosis for diseases with genetic predisposition and nondisease testing. Expert Rev. Mal Diagn. 2(5), 509–513 (2002).
   Google Scholar
• Braude P, Pickering S, Flinter F, Ogilvie CM. Preimplantation genetic diagnosis. Nature Rev Genet. 3(12), 941–953 (2002).
   Google Scholar
• Fallon L, Harton GL, Sisson ME etal Preimplantation genetic diagnosis for spinal muscular atrophy Type I. Neurology53(5), 1087–1090 (1999).
   PubMed Web of Science ®Google Scholar
• Dreesen JC, Bras M, de Die-Smulders C etal Preimplantation genetic diagnosis of spinal muscular atrophy. Mal Hum. Reprod 4(9), 881–885 (1998).
   Web of Science ®Google Scholar
• Blake D, Tan SL, Ao A. Assessment of multiplex fluorescent PCR for screening single cells for trisomy 21 and single gene defects. Mal Hum. Reprod. 5(12), 1166–1175 (1999).
   Google Scholar
• Daniels G, Pettigrew R, Thornhill A etal Six unaffected livebirths following preimplantation diagnosis for spinal muscular atrophy. Mal Hum. Reprod 7(10), 995–1000 (2001).
   Web of Science ®Google Scholar
• Pickering S, Polidoropoulos N, Caller J etal Strategies and outcomes of the first 100 cycles of preimplantation genetic diagnosis at the Guy's and St. Thomas' Center. Perth. Steril 79(1), 81–90 (2003).
   Google Scholar
• Yan H, Papadopoulos N, Marra G eta]. Conversion of diploidy to haploidy. Nature 403(6771), 723–724 (2000).
   PubMedGoogle Scholar
• Mailman MD, Hemingway T, Darsey RL etal Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMNI copies on one chromosome. Hum. Genet. 108(2), 109–115 (2001).
   Google Scholar
• ••Describes methods to detect carriers withtwo SMN 1 copies on one chromosome 5 and a deletion/conversion on the other.
   Google Scholar
• Skordis LA, Duncldey MG, Yue B, Eperon IC, Muntoni E Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SM/V2gene expression in patient fibroblasts. Proc. Natl Acad. Sci. USA 100(7), 4114–4119 (2003).
   Google Scholar
• Kerr DA, Llado J, Shamblott MJ etal Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neurone injury. I Neurosci. 23(12), 5131–5140 (2003).
   Google Scholar
• Wirth B. Spinal muscular atrophy: state-of-the-art and therapeutic perspectives. Amyotroph. Lateral Scler. Other Motor Neumn Disord 3(2), 87–95 (2002).
   Google Scholar
• •Excellent overview of SMA.
   Google Scholar
• Andreassi C, Jarecki J, Zhou J eta]. Aclarubicin treatment restores SMN levels to cells derived from Type I spinal muscular atrophy patients. Hum. Mal Genet. 10(24), 2841–2849 (2001).
   Google Scholar
• Chang JG, Hsieh-Li HM, Jong YJ etal Treatment of spinal muscular atrophy by sodium butyrate. Proc. Natl Acad. Sc]. USA 98(17), 9808–9813 (2001). tti Brichta L, Hofmann Y, Hahnen E et al Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum. Mal Genet. 12(19), 2481–2489 (2003).
   Google Scholar
• DiDonato CJ, Parks RJ, Kothary R. Development of a gene therapy strategy for the restoration of survival motor neurone protein expression: implications for spinal muscular atrophy therapy. Hum. Gene firer. 14(2), 179–188 (2003).
   Google Scholar
• Lesbordes JC, Cifuentes-Diaz C, Miroglio A etal Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy. Hum. Mal Genet. 12(11), 1233–1239 (2003).
   Google Scholar
• Tsai CH, Jong YJ, Hu CJ etal Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families.j Neural Sc]. 190 (1–2), 35–40 (2001).
   Google Scholar
• Skordis LA, Duncldey MG, Burglen L eta]. Characterisation of novel point mutations in the survival motor neurone gene SM/Vin three patients with SMA. Hum. Genet. 108(4), 356–357 (2001).
   Google Scholar
• Brahe C, Clermont 0, Zappata S etal Frameshift mutation in the survival motor neurone gene in a severe case of SMA Type I. Hum. Mal Genet. 5(12), 1971–1976 (1996).
   Google Scholar
• Hahnen E, Schonling J, Rudnik-Schoneborn S etal Missense mutations in exon 6 of the survival motor neurone gene in patients with spinal muscular atrophy (SMA). Hum. Mal Genet. 6(5), 821–825 (1997).
   Google Scholar
• Wang CH, Papendick BD, Bruinsma P, Day JK. Identification of a novel missense mutation of the SMN(77 gene in two siblings with spinal muscular atrophy. Neumgenetics 1(4), 273–276 (1998).
   Google Scholar
• Talbot K, Ponting CP, Theodosiou AM et al Missense mutation clustering in the survival motor neurone gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism? Hum. Mal. Genet. 6(3), 497–500 (1997).
   PubMed Web of Science ®Google Scholar
• Gambardella A, Mazzei R, Toscano A eta]. Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neurone gene. Ann. Neural. 44(5), 836–839 (1998).
   Google Scholar