molecular genetic analysis of survival motor neuron gene in 460 turkish cases with suspicious spinal muscular atrophy disease

how to cite this article: rashnonejad a, onay h, atik t, atan sahin o, gokben s, tekgul h, ozkinay f. molecular genetic analysis of survival motor neuron gene in 460 turkish cases with suspicious spinal muscular atrophy disease. iran j child neurol. autumn 2016; 10(4):30-35. abstract objective to describe 12 yr experience of molecular genetic diagnosis of spinal muscular atrophy (sma) in 460 cases of turkish patients.   materials & methods a retrospective analysis was performed on data from 460 cases, referred to medical genetics laboratory, ege university’s hospital, izmir, turkey, prediagnosed as sma or with family history of sma between 2003 and 2014. the pcr-restriction fragment length polymorphism (rflp) and the multiplex ligation–dependent probe amplification (mlpa) analysis were performed to detect the survival motor neuron (smn)1 deletions and to estimate smn1 and smn2 gene copy numbers.   results using pcr-rflp test, 159 of 324 postnatal and 18 of 77 prenatal cases were detected to have smn1 deletions. from positive samples, 88.13% had a homozygous deletion in both exon 7 and exon 8 of smn1. using mlpa, 54.5% of families revealed heterozygous deletions of smn1, and 2 or 3 copies of smn2, suggesting a healthy sma carrier. among patients referred for sma testing, the annual percentage of patients diagnosed as sma has decreased gradually from 90.62% (2003) down to 20.83% (2014).   conclusion although pcr-rflp method is a reliable test for sma screening, mlpa is a necessary additional test and provide relevant data for genetic counseling of families having previously affected child. the gradual decrease in the percentage of patients molecularly diagnosed as sma shows that clinicians have begun to use genetic tests in the differential diagnosis of muscular atrophies. cost and availability of these genetic tests has greatly attributed to their use.      references 1. brichta l, holker i, haug k, klockgether t, wirth b. in vivo activation of smn in spinal muscular atrophy carriers and patients treated with valprotae. ann neurol 2006;59:970-5. 2. prior tw, krainer ar, hua y, swoboda kj, snyder pc, bridgeman sj, et al. a positive modifier of spinal muscular atrophy in the smn2 gene. am j hum genet 2009;85:408-13. 3. striano p, boccella p, sarappa c, striano s. spinal muscular atrophy and progressive myoclonic epilepsy: one case report and characteristics of the epileptic syndrome. seizure 2004;13:582-6. 4. wirth b. an update of the mutation spectrum of the survival motor neuron gene (smn1) in autosomal recessive spinal muscular atrophy (sma). hum mutat 2000;15:228-37. 5. van der steege g, grootscholten pm, van der vlies p, draaijers tg, osinga j, cobben jm, et al. pcr-based dna test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. lancet 1995;345:985-6. 6. rekik i, boukhris a, ketata s, amri m, essid n, feki i, et al. deletion analysis of smn and naip genes in tunisian patients with spinal muscular atrophy. ann indian acad neurol 2013;16:57-61. 7. de souza godinho fm, bock h, gheno tc, saraiva-pereira ml. molecular analysis of spinal muscular atrophy: a genotyping protocol based on taqman realtime pcr. genet mol biol 2012;35:955-9. 8. burghes ah. when deletion is not a deletion? when it is converted? am j hum genet 1997;61:9-15. 9. kubo y, nishio h, saito k. a new method for smn1 and hybrid smn gene analysis 1. in spinal muscular atrophy using long-range pcr followed by sequencing. j hum 2. genet 2015;60:233-9. 10. ogino s, leonard dg, rennert h, wilson rb. spinal muscular atrophy genetic testing experience at an academic medical center. j mol diagn 2002;4:53-8. 11. baumbach-reardon l, sacharow s, ahearn me. spinal muscular atrophy, x-linked infantile. gene review 1993. 12. khaniani ms, derakhshan sm, abasalizadeh s. prenatal diagnosis of spinal muscular atrophy: clinical experience and molecular genetics of smn gene analysis in 36 cases. j prenat med 2013;7:32-4. 13. lin sp, chang jg, jong yj, yang ty, tsai ch, wang nm, et al. prenatal prediction of spinal muscular atrophy in chinese. prenat diagn 1999;19:657-61. 14. cobben jm, scheffer h, de visser m, van der steege g, verhey jb, osigna j, et al. prenatal prediction of spinal muscular atrophy. experience with linkage studies and consequences of present smn deletion analysis. eur j hum genet 1996;4:231-6. 15. miskovic m, lalic t, radivojevic d, cirkovic s, ostojic s, guc-scekic m. ten years of experience in molecular prenatal diagnosis and carrier testing for spinal muscular atrophy among families from serbia. int j gynaecol obstet 2014;124:55-8. 16. mailman md, heinz jw, papp ac, snyder pj, sedra ms, burghes ahm, wirth b, prior tw. molecular analysis of spinal muscular atrophy and modification of the phenotype by smn2. genet med 2002;4:20–26. 17. ogino s, leonard dg, rennert h, ewens wj, wilson rb. genetic risk assessment in carrier testing for spinal muscular atrophy. am j med genet 2002;110:301-7. 18. wirth b. an update on the mutation spectrum of the survival motor neuron gene (smn1) in autosomal recessive spinal muscular atrophy (sma). hum mutat 2000;15:228–37.