Function Of Point Mutations In PLP1 Gene Of Pei Mei’s Disease

ObjectPelizaeus–Merzbacher disease (PMD) is an X-linked recessive condition diffuse whitematter damage disease，which is caused by alterations of the proteolipid protein 1 (PLP1) geneon chromosome Xq22.2, including duplications, triplications, point mutations and deletions ofthe gene. These can lead to myelination abnormalities and(or) oligodendrocyte cell death andlack or reduction of the extensive white matter region of myelin.The study proves thatc.353C>G(p.T117R) c.467C>T(p.T156I) c.517C>T(p.P173S) c.623G>T(p.G208V)c.646C>T(p.P216S) c.709T>G(p.F237V) A242V，which allare the point mutations of the PLP1can lead to PMD pathogenic mutation.MethodThe children which is clinical diagnosed PMD were carried out genetic diagnosis to find outdenovel point mutations and construct mutation plasmid.Then mutation plasmids weretransferred to the corresponding cells by Chemical transfection.Thenobserving mutation plasmids influence U373MG cell activity by MTT and extracting protein ofmutation plasmids,which were transferred into MO3.13,And observing protein expression ofmutation plasmids by Western blot.ResultThe first Wild-type plasmid does not influence the activity of U373MG cells, while the remaining mutants effect and c.353C>G(p.T117R) c.467C>T(p.T156I) c.623G>T(p.G208V)c.646C>T(p.P216S) c.709T>G(p.F237V) A242V greater impact than c.517C>T(p.P173S)The second c.353C>G(p.T117R) c.467C>T(p.T156I) c.517C>T(p.P173S) c.623G>T(p.G208V)c.646C>T(p.P216S) c.709T>G(p.F237V) A242V mutation protein expression in varydecline.Conclusionc.353C>G(p.T117R) c.467C>T(p.T156I) c.517C>T(p.P173S) c.623G>T(p.G208V)c.646C>T(p.P216S) c.709T>G(p.F237V) A242Vall are pathogenic mutations of PMD.