SACİDE PEHLİVAN, Ferda ÖZKINAY, SAVAŞ İZZETOĞLU, Özgür ÇOĞULU, Arife KUNT, TUFAN ÇANKAYA, Eren DEMİRTAŞ, Sarenur TÜTÜNCÜOĞLU

Spinal müsküler atrofi'de moleküler tanı: Ege bölgerinde bir referans merkezindeki uygulamalar

Spinal Müsküler Atrofi (SMA) dünyada sık görülen, otozomal resesif geçişli nörodejeneratif bir hastalıktır. Bu çalışmada, çocuk nörologları tarafından SMA tanısı konan 18 hastada telomerik-Survival Motor Nöron (tSMN) ve Nöral Apoptosi İnhibitör Proteini (NAİP) gen delesyon analizleri yapılmıştır. Onsekiz hastanın 8'inde hem tSMN geni ekzon 7 ve 8 hem de NAİP geni ekzon 6 delesyonu saptanmıştır. Altı hastada tSMN geni ekzon 7 ve 8 delesyonları gözlenirken, kardeş olan 2 hastada yalnız tSMN geni ekzon 7 delesyonu bulunmuş fakat ekzon 8 delesyonu görülmemiştir. İki hastada her 2 gende analizi yapılan ekzonlarda delesyon saptanmamıştır.

Anahtar Kelimeler:

Nörodejeneratif hastalıklar, Tanı teknik ve işlemleri, Gen parçası kaybı, Kas atrofisi, spinal

Molecular diagnosis in spinal muscular atrophy: Applications at a reference center in Aegean region

Spinal Muscular Atrophy (SMA) neurodegenerative disorde (SMA) is one of the most common autosomal recessive neurodegenerative disorders. In this study, 18 patients diagnosed to have SMA by pediatric neurologist were investigated for telomeric-Survival Motor Neuron (tSMN) and Neuronal Apoptosis Inhibitory Protein (NAIP) gene deletions. Among 18 patients, 8 had both exon 7 and 8 deletions of SMN gene and exon 6 deletion of NAIP gene. Six patients had exon 7 and 8 deletions of tSMN. Two patients who were sibling had only exon 7 deletions of tSMN gene. In two patients out of 18 patients no deletion could be detected in the genes investigated.

Keywords:

Neurodegenerative Diseases, Diagnostic Techniques and Procedures, Gene Deletion, Muscular Atrophy, Spinal,

PDF

___

1. Pearn JH. Incidence, prevalence and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet 1978; 15: 409-413.
2. Munsat TL. Workshop report international SMA collaboration. Neuromusc Disord 1991; 1: 81.
3. Dubovvitz V. Chaos in classification of the spinal muscular atrophies in ohildhood. Neuromusc Disord 1991; 1: 77-78.
4. Davies KE, Thomas NH, Danielz RJ, et al. Molecular studies of spinal muscular atrophy. Neuromusc Disord 1991; 1: 83-85.
5. Cunningham M, and Stocks J. Werding-Hoffmann disease. Arch Dis Child 1978; 53: 921-925.
6. Lefebre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Celi 1995; 80: 155-165.
7. Van der Steege G, Grootscholten PM, Van der Vlies P, et al. PCR - based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet 1995; 345: 985-986.
8. Roy N, Mahadevan MS, McLean M, et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Celi 1995; 80: 167-178
9. Christodoulou K, Kyriakides T, Hristova AH, et al. Mapping of distal form of spinal muscular atrophy with upper limb predomonance to chromosome 7p. Hum Mol Genet 1995; 4: 1629-1632.
10. Isozumi K, DeLong R, Kaplan J, et al. Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31. Hum Mol Genet 1996; 5: 1377-1382.
11. Mhatre AN, Trifiro MA Kaufmann M, et al. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genet 1993; 5: 184-188.
12. Yapicakis C, Kapaki E, Boussiou M, et al. Prenatal diagnosis of X - linked spinal and bulbar muscular atrophy. Prenatal Diagnos 1996; 16:262-265.
13. Miller SA, and Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 1988; 28: 1215.
14. H.Erdem, S.Pehlivan, H.Topaloğlu, M.Özgüç. Deletion analysis in Turkish spinal muscular atrophy patients. Brain and Development. 1999; 37 (2): 167-170.
15. Maniatis T, Fritsch EF, Sambrook F, Molecular Cloning a Laboratory Manuel, Cold Spring Harbor Laboratory; USA, 1983.
16. Morrison KE. Advances in SMA research: Revievv of gene deletions. Neuromusc Disord 1996; 6: 397-408.
17. Hahnen E, Schöling J, Rudnic-Schöneborn S, et al. 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, 1995; 59; 1057-1065.
18. Scheffer H, Cobben JM, Matthiss, Wİrth B. Best practice guidelines for molecular analysis in spinal muscular atrophy. Eur J Hum Genet 2001; 9 (7): 484-491.