engleski

Molecular diagnostics of spinal muscular atrophy by determination of copy numbers of SMN1, SMN2 and NAIP genes

Aim: SMA is autosomal recessive disease with 1/10000 livebirths. 95% SMA patients are homozygous for exon 7 SMN1 deletion, 3.6% are compound heterozygous (with point mutation). SMA carriers are heterozygous with one exon 7 SMN1 copy. Methods: We determined SMN1, SMN2 and NAIP copy number using MLPA/capillary electrophoresis. Results: Analysis of 222 DNA samples revealed 27 SMA carriers, 21 SMA patients and 174 persons with 2 SMN1 copies. Compared to group of 174 individuals: SMA carriers and SMA patients number with 3 SMN2 copies is increased ; SMA carriers and SMA patients number with 1 SMN2 copy is decreased ; SMA patients number with 2 SMN2 copies is decreased ; we detected 4.76% individuals with 4 SMN2 copies ; SMA carriers and SMA patients number with 1 NAIP copy is increased ; SMA carriers and SMA patients number with 2 NAIP copies is decreased ; SMA carriers number with 3 NAIP copies is decreased ; we detected absence of SMA carriers with 4 NAIP copies as well as SMA patients with 3 and 4 NAIP copies ; we detected 0 NAIP copies in 33.33% SMA patients and in 3.7% SMA carriers. Conclusion: Majority of SMA patients are homozygous for deletion of SMN1 and a normal or reduced number of SMN2 copies. Majority of type II and III SMA patients show homozygous absence of SMN1 as a result of gene conversion of SMN1 into SMN2, leading to absence of functional SMN1 and an increase to 3-4 copies of SMN2. NAIP deletions may indicate a severe form of SMA.

SMA; SMN1; SMN2; NAIP

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