Quantitative analysis of survival motor neuron copies: Identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype- phenotype correlation, and implications for genetic counseling

American Journal of Human Genetics

Volumn 64, Issue 5, 1999, Pages 1340-1356

  Wirth, Brunhilde ^a,c   Herz, M ^a   Wetter, A ^a   Moskau, S ^a   Hahnen, E ^a   Rudnik Schoneborn S ^a   Wienker, T ^a   Zerres, K ^a,b  

^a UNIVERSITY OF BONN   (Germany)

^b RWTH AACHEN UNIVERSITY   (Germany)

^c UNIVERSITY HOSPITAL BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; RNA;

ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; FRAMESHIFT MUTATION; GENE; GENE MUTATION; GENE SEQUENCE; GENETIC COUNSELING; GENOTYPE; HAPLOTYPE; HUMAN; HUMAN CELL; INTRON; MISSENSE MUTATION; MOTONEURON; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPINAL MUSCULAR ATROPHY;

EID: 0033358719     PISSN: 00029297     EISSN: None     Source Type: Journal    
DOI: 10.1086/302369     Document Type: Article

References (52)

1. Brahe C, Clermont O, Zappata S, Tiziano F, Melki J, Neri G (1996) Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I. Hum Mol Genet 5: 1971-1976
2. Burghes AHM (1997) When is a deletion not a deletion? When it is converted. Am J Hum Genet 61:9-15
3. Bürglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, et al (1996a) Structure and organization of the human survival motor neuron (SMN) gene. Genomics 32:479-482
4. Bürglen L, Patel S, Dubowitz V, Melki J, Muntoni A (1996b). A novel point mutation in the SMN gene in a patient with type III spinal muscular atrophy. First Congress of the World Muscle Society 1996, Elsevier, S39
5. Bürglen L, Seroz T, Minou P, Lefebvre S, Burlet P, Munnich A, Pequignot EV, et al (1997) The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease. Am J Hum Genet 60:72-79
6. Bussaglia E, Clermont O, Tizzano E, Lefevbre S, Bürglen L, Cruaud C, Urtizberea JA, et al ( 1995) A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nat Genet 11:335-337
7. Campbell L, Danilies RJ, Dubowitz V, Davies KE (1998) Maternal mosaicism for a second mutational event in a type I spinal muscular atrophy family. Am J Hum Genet 63:37-44
8. Campbell L, Potter A, Ignatius J, Dubowitz V, Davies K (1997) Genomics variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotypes. Am J Hum Genet 61:40-50
9. Carter TA, Bönnemann CG, Wang CH, Obici S, Parano E, Fatima Bonaldo de M, Ross BM, et al (1997) A multicopy transcription-repair gene, BTF2p44, maps to the region and demonstrates SMA associated deletions. Hum Mol Genet 6: 229-236
10. Chang JG, Jong YJ, Huang JM, Wang WS, Yang TY, Chang CP, Chen YJ, etal (1995) Molecular bases of spinal muscular atrophy in Chinese. Am J Hum Genet 57:1503-1505
11. Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan JY, Kang X, Lefebvre C, et al (1998) Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP. Genomics 48: 121-127
12. Cobben JM, Steege van der G, Grootscholten P, Visser de M, Scheffer H, Buys CHCM (1995) Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy. Am J Hum Genet 57:805-808
13. Collier S, Tassabehji M, Sinnott P, Strachan T (1993) A de novo pathological point mutation at the 21-hydroxylase locus: implications for gene conversion in the human genome. Nat Genet 3:260-265
14. DiDonato CJ, Ingraham SE, Mendell JR, Prior TW, Lenard S, Moxley RT, Florence J, et al (1997) Deletion and conversion in SMA patients: is there a relationship to severity? Ann Neurol 41:230-237
15. DiDonato CJ, Morgan K, Carpten JD, Fuerst P, Ingraham SE, Prescott G, McPherson JD, et al (1994) Association between Ag1-CA alleles and severity of autosomal recessive proximal spinal muscular atrophy. Am J Hum Genet 55:1218-1229
16. Fischer U, Liu Q, Dreyfuss G (1997) The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90:1023-1029
17. Hahnen E, Forkert R, Marke C, Rudnik-Schöneborn S, Zerres K, Wirth B (1995) Molecular analysis of SMA 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 4: 1927-1933
18. Hahnen E, Schönling J, Rudnik-Schöneborn J, Zerres K, Wirth B (1996) Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease. Am J Hum Genet 59:1057-1065
19. _ (1997) Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA). Hum Mol Genet 6:821-825
20. Harteveld KL, Losekoot M, Fodde R, Giordano PC, Bernini LF (1997) The involvement of Alu repeats in recombination events at the α-globin gene cluster: characterization of two α-thalassaemia deletion breakpoints. Hum Genet 99: 528-534
21. International SMA Consortium (1992) Meeting report: International SMA Consortium Meeting. Neuromusc Disord 2: 423-428
22. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, et al (1995) Identification and characterization of the spinal muscular atrophy determining gene. Cell 80:155-165
23. Liu Q, Fischer U, Wang F, Dreyfuss G (1997) The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell 90:1013-1021
24. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in exon 7 of the survival motor neuron (SMN) gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA (in press)
25. Lorson CL, Strasswimmer J, Yao L-M, Baleja J, Hahnen E, Wirth B, Le T, et al (1998) SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 19:63-67
26. McAndrew PE, Parsons DW, Simard LR, Rochette C, Ray PN, Mendell J, Prior TW, et al (1997) Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNt and SMNc gene copy number. Am J Hum Genet 60: 1411-1422
27. Melki J, Lefebvre S, Bürglen L, Burlet P, Clermont O, Millasseau P, Reboullet S, et al (1994) De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science 264:1474-1477
28. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
29. Nyström-Lahti M, Kristo P, Nicolaides NC, Chang S-Y, Aaltonen LA, Moisio AL, Jarvinen H, et al (1995) Founder mutations and Alu-mediated recombination in hereditary colon cancer. Nat Med 1:1203-1206
30. Parsons DW, McAndrew PE, Allison PS, Parker WD Jr, Burghes AHM, Prior TW (1998) Diagnosis of spinal muscular atrophy in an SMN non-deletion patient using a quantitative PCR screen and mutation analysis. J Med Genet 35: 674-676
31. Parsons DW, McAndrew PE, Monani UR, Mendell JR, Burghes AH, Prior TW (1996) An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene. Hum Mol Genet 5: 1727-1732
32. Patrinos GP, Kollia P, Loutradi-Anagnostou A, Loukopoulos D, Papadakis MN (1998) The Cretan type of non-deletional hereditary persistence of fetal hemoglobin [A gamma-158C→T] results from two independent gene conversion events. Hum Genet 102:629-634
33. Petrij-Bosch A, Peelen T, Vliet v M, Eijk van R, Olmer R, Drüsedau M, Hogervorst FBL, et al (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 17:341-345
34. Raclin V, Veber PS, Bürglen L, Munnich A, Melki J (1997) de novo deletions in spinal muscular atrophy: implications for genetic counselling. J Med Genet 34:86-87
35. Rochette CF, Surh LC, Ray PN, McAndrew PE, Prior TW, Burghes AHM, Vanasse M, et al (1997) Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7. Neurogenetics 1:141-147
36. Rodrigues NR, Owen N, Talbot K, Ignatius J, Dubowitz V, Davies KE (1995) Deletions in the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum Mol Genet 4:631-634
37. Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, et al (1995) The gene for neuronal apoptosis inhibitory protein (NAIP), a novel protein with homology to baculoviral inhibitors of apoptosis, is partially deleted in individuals with type 1, 2, and 3 spinal muscular atrophy (SMA). Cell 80:167-178
38. Rüdiger NS, Gregersen N, Kieland-Brandt MC (1995) One short well conserved region of Alu-sequences is involved in human gene rearrangements and has homology with prokaryotic chi. Nucleic Acids Res 23:256-260
39. SAS Institute (1996) SAS/STAT User's Guide, Release 6.6 Edition, Cary, NC
40. Scharf JM, Endrizzi MG, Wetter A, Huang S, Thompson TG, Dietrich WF, Wirth B, et al (1998) Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics. Nat Genet 20:83-86
41. Schrank B, Götz R, Gunnersen JM, Ure JM, Toyka KV, Schmith AG, Sendtner M (1997) Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci USA 94:9920-9925
42. Simard LR, Rochette C, Semionov A, Morgan K, Vanasse M (1997) SMN(T) and NAIP mutations in Canadian families with spinal muscular atrophy (SMA): genotype/phenotype correlation with disease severity. Am J Med Genet 72:51-58
43. Talbot K, Ponting CP, Theodosiou AM, Rodrigues NR, Surtees R, Mountford R, Davies KE (1997) 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 Mol Genet 6:497-500
44. Velasco E, Valero C, Valero A, Moreno F, Hernandez-Chico C (1996) Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype. Hum Mol Genet 5:257-263
45. van der Steege G, Grootscholten PM, Cobben JM, Zappata S, Scheffer H, Dunnen den JT, Ommen van G-J B, et al (1996) Apparent gene conversion involving the SMN gene in the region of spinal muscular atrophy locus on chromosome 5. Am J Hum Genet 59:834-838
46. van der Steege G, Grootscholten PM, van der Vlies P, Draaijers TG, Osinga J, Cobben JM, Scheffer H, et al (1995) PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet 345:985-986
47. Wang CH, Papendick BD, Bruinsma P, Day JK (1998) Identification of a novel missense mutation of the SMNt gene in two siblings with spinal muscular atrophy. Neurogenetics 1: 273-276
48. Wang CH, Xu J, Carter TA, Ross BM, Dominski MK, Bellcross CA, Penchaszadeh GK, et al (1996) Characterization of survival motor neuron (SMNt) gene deletions in asymptomatic carriers of spinal muscular atrophy. Hum Mol Genet 5: 359-365
49. Wirth B, Hahnen E, Morgan K, DiDonato CJ, Dadze A, Rudnik-Schöneborn S, Simard L R, et al (1995) Allelic association and deletions in autosomal recessive proximal spinal muscular atrophy: Association of marker genotype to disease severity and candidate cDNAs. Hum Mol Genet 4: 1273-1284
50. Wirth B, Schmidt T, Hahnen E, Rudnik-Schöneborn S, Krawczak M, Müller-Myhsok B, Schönling J, et al (1997) De novo rearrangements found in 2% of index patients with spinal muscular atrophy (SMA): mutational mechanisms, parental origin, mutation rate and implications for prenatal diagnosis. Am J Hum Genet 61:1102-1111
51. Zerres K, Rudnik-Schöneborn S (1995) Natural history in proximal spinal muscular atrophy (SMA): clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 52:518-523
52. Zielenski J, Rozmahel R, Bozon D, Kerem B, Grzelczak Z, Riordan JR, Rommens J, et al (1991) Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics 10:214-228