Novi uvid u genetiku naslednih perifernih neuropatija
Genetics of inherited peripheral neuropathies: renewed data
dc.contributor | Pavlović, Sonja | |
dc.creator | Keckarević Marković, Milica | |
dc.creator | Kecmanović, Miljana | |
dc.creator | Keckarević, Dušan | |
dc.date.accessioned | 2023-04-27T12:12:01Z | |
dc.date.available | 2023-04-27T12:12:01Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 2787-2947 | |
dc.identifier.uri | https://imagine.imgge.bg.ac.rs/handle/123456789/1812 | |
dc.description.abstract | Nasledne periferne neuropatije čini klinički i genetički heterogena grupa bolesti uzrokovanih aksonalnom degeneracijom motornih i senzornih neurona perifernog nervnog sistema. Odlikuju se izrazitom alelskom i lokusnom heterogenošću, a do danas je sa ovom grupom bolesti asocirano više od 1000 mutacija u preko 100 gena. Korišćenjem klasičnih metoda genetičke dijagnostike najveći broj uzročnih mutacija identifikovan je u 4 gena: PMP22, GJB1, MFN2 i MPZ. Najučestaliji tip, CMT1A, uzrokovan je duplikacijom 1,5 Mb u regionu hromozoma 17p11.2 i čini oko 50% svih naslednih perifernih neuropatija. Ovom duplikacijom obuhvaćen je gen PMP22 koji kodira protein mijelinskog omotača. Recipročna delecija ovog regiona asocirana je sa blagom naslednom neuropatijom. Geni GJB1, MFN2 i MPZ se karakterišu širokim spektrom mutacija, a populacione specifičnosti u vidu značajnih odstupanja u zastupljenosti pojedinih mutacija se mogu objasniti efektom osnivača. Upotrebom masivnog paralelnog sekvenciranja omogućen je napredak u genetičkoj dijagnostici ovih bolesti koji se pre svega ogleda u otkriću novih gena, kao i u otkriću novih mutacija u genima odranije asociranim sa ovim, ali i sa drugim neurološkim i mišićnim bolestima. Pri tome, verovatnoća za otkrivanje uzročne mutacije koreliše sa pozitivnom porodičnom anamnezom, prisustvom endogamije, ranim početkom i demijelinirajućim oblikom bolesti. Takođe, kod nekih bolesnika je identifikovano i prisustvo strukturnih varijacija koje ne obuhvataju do sada poznate uzroke naslednih perifernih neuropatija, kod kojih je patomehanizam nastanka bolesti i dalje nepoznat. | sr |
dc.description.abstract | Inherited peripheral neuropathies (IPN) comprise a clinicaly and geneticaly heterogenous group of disorders caused by axonal degeneration of motor and sensory nerves of peripheral nervous system. So far, more than 1000 mutations in more then 100 genes has been found to be associated with IPN. Using standard molecular-genetic diagnostics, vast number of mutations was identified in following genes: PMP22, GJB1, MFN2 and MPZ. The most frequent, CMT1A, is caused by 1,5 Mbp duplication of 17p11.2 and represents aproximatelly 50% of all IPN. The duplication includes myelin sheet protein gene PMP22, whereas reciprocal deletion is associated with a mild hereditary neuropathy termed HNPP. GJB1, MFN2 and MPZ genes harbour various mutations, whose frequencies vary between populations. Significant differences of individual mutation frequencies could be mostly explained by founder effect. Massive parallel sequencing methodologies (MPS) brought new discoveries. First of all, new genes were found to be associated with IPN. Then, new mutations in well-known genes previously associated with IPN, but also with other neurological and muscular disorders, were found to be disease-causing. Also, some patients were found to carry structural variants involving regions not previously associated with IPN, with pathomechanism of the disease yet to be resolved. Generally, a positive genetic diagnosis was more likely to be reached in cases with positive history of neuropathy and consanguinity, early onset and/or demyelinating neuropathy. | sr |
dc.language.iso | sr | sr |
dc.publisher | Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo | sr |
dc.rights | openAccess | sr |
dc.source | Trendovi u molekularnoj Biologiji | sr |
dc.subject | nasledne periferne neuropatije | sr |
dc.subject | masivno paralelno sekvenciranje | sr |
dc.subject | strukturne varijacije | sr |
dc.subject | Inherited peripheral neuropathy | sr |
dc.subject | massive parallel sequencing | sr |
dc.subject | structural variants | sr |
dc.title | Novi uvid u genetiku naslednih perifernih neuropatija | sr |
dc.title | Genetics of inherited peripheral neuropathies: renewed data | sr |
dc.type | bookPart | sr |
dc.rights.license | ARR | sr |
dc.citation.epage | 61 | |
dc.citation.issue | 2 | |
dc.citation.spage | 51 | |
dc.identifier.fulltext | https://imagine.imgge.bg.ac.rs/bitstream/id/174327/Genetics_of_inherited_peripheral_neuropathies_renewed_data_2022.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_imagine_1812 | |
dc.type.version | publishedVersion | sr |
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Trendovi u molekularnoj biologiji / Trends in Molecular Biology
Tematski zbornik je imao za cilj da prikaže koje su teme obeležile istraživanja iz molekularne biologije u Srbiji i u svetu.