Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy

Overview

Journal J Neurodegener Dis

Date 2015 Aug 29

PMID 26317002

Citations 2

Authors

Y Sifi

K Sifi

A Boulefkhad

N Abadi

Z Bouderda

R Cheriet

M Magen

J P Bonnefont

A Munnich

C Benlatreche

A Hamri

Affiliations

Soon will be listed here.

Abstract

Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disorder. It is divided into the acute Werdnig-Hoffmann disease (type I), the intermediate form (type II), the Kugelberg-Welander disease (type III), and the adult form (type IV). The gene involved in all four forms of SMA, the so-called survival motor neuron (SMN) gene, is duplicated, with a telomeric (tel SMN or SMN1) and a centromeric copy (cent SMN or SMN2). SMN1 is homozygously deleted in over 95% of SMA patients. Another candidate gene in SMA is the neuronal apoptosis inhibitory protein (NAIP) gene; it shows homozygous deletions in 45-67% of type I and 20-42% of type II/type III patients. Here we studied the SMN and NAIP genes in 92 Algerian SMA patients (20 type I, 16 type II, 53 type III, and 3 type IV) from 57 unrelated families, using a semiquantitative PCR approach. Homozygous deletions of SMN1 exons 7 and/or 8 were found in 75% of the families. Deletions of exon 4 and/or 5 of the NAIP gene were found in around 25%. Conversely, the quantitative analysis of SMN2 copies showed a significant correlation between SMN2 copy number and the type of SMA.

Citing Articles

The impact of three gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review.

Dosi C, Masson R Front Neurol. 2024; 15:1308296.

PMID: 38487326 PMC: 10937544. DOI: 10.3389/fneur.2024.1308296.

A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans.

Mahungu A, Monnakgotla N, Nel M, Heckmann J Orphanet J Rare Dis. 2022; 17(1):133.

PMID: 35331287 PMC: 8944057. DOI: 10.1186/s13023-022-02280-2.

References

Glotov A, Kiselev A, Ivashchenko T, Baranov V . [Analysis of deletional damage in SMN1, SMN2, and NAIP genes in patients with spinal muscular atrophy in the northwestern region of Russia]. Genetika. 2001; 37(8):1156-9. View

Ogino S, Gao S, Leonard D, Paessler M, Wilson R . Inverse correlation between SMN1 and SMN2 copy numbers: evidence for gene conversion from SMN2 to SMN1. Eur J Hum Genet. 2003; 11(3):275-7. DOI: 10.1038/sj.ejhg.5200957. View

Monani U, Lorson C, Parsons D, Prior T, Androphy E, Burghes A . A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999; 8(7):1177-83. DOI: 10.1093/hmg/8.7.1177. View

Gilliam T, Brzustowicz L, Castilla L, Lehner T, Penchaszadeh G, Daniels R . Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature. 1990; 345(6278):823-5. DOI: 10.1038/345823a0. View

Al Rajeh S, Majumdar R, Awada A, Adeyokunnu A, Al Jumah M, al Bunyan M . Molecular analysis of the SMN and NAIP genes in Saudi spinal muscular atrophy patients. J Neurol Sci. 1998; 158(1):43-6. DOI: 10.1016/s0022-510x(98)00053-7. View

Taylor J, Thomas N, Lewis C, Abbs S, Rodrigues N, Davies K . Correlation of SMNt and SMNc gene copy number with age of onset and survival in spinal muscular atrophy. Eur J Hum Genet. 1998; 6(5):467-74. DOI: 10.1038/sj.ejhg.5200210. View

Humphrey E, Fuller H, Morris G . Current research on SMN protein and treatment strategies for spinal muscular atrophy. Neuromuscul Disord. 2011; 22(2):193-7. DOI: 10.1016/j.nmd.2011.06.002. View

Rodrigues N, Owen N, Talbot K, Patel S, Muntoni F, Ignatius J . Gene deletions in spinal muscular atrophy. J Med Genet. 1996; 33(2):93-6. PMC: 1051831. DOI: 10.1136/jmg.33.2.93. View

Biros I, Forrest S . Spinal muscular atrophy: untangling the knot?. J Med Genet. 1999; 36(1):1-8. PMC: 1762953. View

10.

Srivastava S, Mukherjee M, Panigrahi I, Shanker Pandey G, Pradhan S, Mittal B . SMN2-deletion in childhood-onset spinal muscular atrophy. Am J Med Genet. 2001; 101(3):198-202. DOI: 10.1002/ajmg.1386. View

11.

Dubowitz V . Muscle disorders in childhood. Major Probl Clin Pediatr. 1978; 16:iii-xiii, 1-282. View

12.

Velasco E, Valero C, Valero A, Moreno F, Hernandez-Chico C . 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. 1996; 5(2):257-63. DOI: 10.1093/hmg/5.2.257. View

13.

Cobben J, van der Steege G, Grootscholten P, de Visser M, Scheffer H, Buys C . Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy. Am J Hum Genet. 1995; 57(4):805-8. PMC: 1801497. View

14.

Wirth B, Herz M, Wetter A, Moskau S, Hahnen E, Rudnik-Schoneborn S . 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. Am J Hum Genet. 1999; 64(5):1340-56. PMC: 1377870. DOI: 10.1086/302369. View

15.

Burlet P, Burglen L, Clermont O, Lefebvre S, Viollet L, Munnich A . Large scale deletions of the 5q13 region are specific to Werdnig-Hoffmann disease. J Med Genet. 1996; 33(4):281-3. PMC: 1050575. DOI: 10.1136/jmg.33.4.281. View

16.

Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A . Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet. 1997; 16(3):265-9. DOI: 10.1038/ng0797-265. View

17.

Kesari A, Misra U, Kalita J, Mishra V, Pradhan S, Patil S . Study of survival of motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) gene deletions in SMA patients. J Neurol. 2005; 252(6):667-71. DOI: 10.1007/s00415-005-0714-2. View

18.

Wirth B, Schmidt T, Hahnen E, Rudnik-Schoneborn S, Krawczak M, Muller-Myhsok B . De novo 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. 1997; 61(5):1102-11. PMC: 1716038. DOI: 10.1086/301608. View

19.

Zerres K, Rudnik-Schoneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I . A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. 1997; 146(1):67-72. DOI: 10.1016/s0022-510x(96)00284-5. View

20.

Bussaglia E, Clermont O, Tizzano E, Lefebvre S, Burglen L, Cruaud C . A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nat Genet. 1995; 11(3):335-7. DOI: 10.1038/ng1195-335. View