Search

Spinalne amiotrofije su klinički heterogena skupina nasljednih bolesti, najčešće recesivnih, uzrokovana degeneracijom stanica prednjih rogova kičmene moždine. Dva su gena kandidata za uzročnika bolesti: gen za preživljavanje motornih neurona (SMN) i gen za proteinski inhibitor neuralne apoptoze (NAIP). Prikazujemo rezultate ispitivanja učestalosti homozigotne delecije u različitih bolesbika uključujući 202 djece s dijagnozom SMA i 70 odraslih bolesnika u skladu s dijagnostičkim kriterijima međunarodnog Konzorcija za SMA. Pretraživanje (screening) delecije eksona 7 i 8, SMN gena obavljeno je PCR/polimorfizmom restrikcijskig fragmenata, zasnovanom na redoslijedu nukleotida između SMN gena i lokusa BCD541. Analiza NAIP gena učinjena je umnažanjem eksona 5 i 13, uz pomoć M-PCR. Rezultati analize bolesnika sa SMA tip I pokazuju delecije eksona 7 i 8, SMN gena, i eksona 5 NAIP gena. Bolesnici sa SMA tipovima II i III pokazuju deleciju eksona 7 i/ili 8 SMN gena, uz normalan nalaz NAIP gena. Međutim, delecija SMN gena nađena je i u SMA tip 4, u kojeg je početak bolesti u odrasloj dobi. Prikazani su i rezultati 20 slučajeva prenatalne dijagnostike. Molekulsko ispitivanje SMN i NAIP gena potvrđuje dijagnostičku važnost pretrage te pomaže razumijevanju molekulske osnove tih genetski sličnih, a klinički različitih bolesti.

Plasmapheresis...

Two genes, i.e. survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) have been mapped to the SMA region of chromosome 5q13. Both genes are frequently deleted or truncated in SMA patients. We have studied 26 patients with SMA types I-III, 29 first relatives, and 14 subjects with mild adult-onset type IV. DNA deletion genotypes were determined by PCR techniques amplifying exons 7 and 8 of SMN, and exon 5 of NAIP gene which distinguish SMN and NAIP telomeric copy from a non-pathogenic gene homologue as a centromeric copy. Results revealed the homozygous deletions of exon 7 and 8 of the SMN gene and exon 5 of the NAIP gene in 3/3 infants with SMA I and in 1/20 with SMA type II. Exons 7 and 8 of the SMN gene were homozygously deleted in 10/20 and only exon 7 in 6/20 children with SMA type II. The overall percentage of deletion cases observed was 77% in children with SMA types I-III. Adult patients with type IV SMA showed no homozygous deletion of exons 7, 8 and 5 of the SMN and NAIP genes. Also, all relatives had both a telomeric and centromeric SMN and NAIP copy. Deletion analysis of SMN and NAIP genes are a significant diagnostic tool, because there are clinical entities resembling SMA which most likely have another pathogenetic background.

nm