本文選題：粘脂貯積癥 + 連鎖分析��； 參考：《華中科技大學(xué)》2009年碩士論文

【摘要】：粘脂貯積癥三型是一種溶酶體貯積病,是溶酶體酶N-乙�；�-1-磷酸轉(zhuǎn)移酶(GlcNAc -phosphotransferase, GlcNAc-PT)活性缺失使得溶酶體酶不能正常進(jìn)入溶酶體的常染色體隱性遺傳病。GlcNAc-PT蛋白以復(fù)合體形式存在,其中α/β亞基由GNPTAB基因編碼,γ亞基由GNPTAG基因編碼。在這一研究中,我們收集了一個(gè)有四代人的中國(guó)人家系,其中有四人患有粘脂貯積癥。連鎖分析顯示這個(gè)中國(guó)家系的致病基因和12號(hào)染色體上的Marker D20S346連鎖。已報(bào)道的致病基因GNPTAB正座位于此位置。通過對(duì)GNPTAB的測(cè)序分析,在這一家系中發(fā)現(xiàn)了一個(gè)雜合的突變,一個(gè)為已報(bào)道的剪切突變IVS13+1GA(C.2715+GA),另一個(gè)為新發(fā)現(xiàn)的無義突變p.R364X(c.1090CT)。這個(gè)家系的四個(gè)病人都帶有這兩個(gè)突變。這個(gè)家系中的其他正常人與226個(gè)正常人對(duì)照中也未發(fā)現(xiàn)該突變的存在。根據(jù)以前的報(bào)道,剪切突變IVS13+1GA(c.2715+1GA)使得該基因轉(zhuǎn)錄時(shí)跳過13號(hào)外顯子的1103bp堿基,導(dǎo)致剪接直接由12號(hào)外顯子到14號(hào)外顯子。新發(fā)現(xiàn)的無義突變p.R364X(c.1090CT)使得GNPTAB基因的α亞基編碼的蛋白截短,從而產(chǎn)生了一個(gè)截短的α亞基編碼蛋白而β亞基編碼蛋白的完全丟失。這一研究是第一次在中國(guó)人群中報(bào)道的GNPTAB基因雜合型突變導(dǎo)致MLⅢ,并且拓寬了GNPTAB導(dǎo)致MLⅢ的突變譜。對(duì)這兩個(gè)突變的進(jìn)一步研究有助于我們更好的理解GNPTAB的基因功能,以及GNPTAB突變和MLⅢ疾病表型之間的關(guān)系。
[Abstract]:Mucolipidosis type III is a lysosomal storage disease. The absence of lysosomal enzyme GlcNAc -phosphotransferase (GlcNAc-PTT) makes lysosomal enzymes not normally enter the lysosomal autosomal recessive hereditary disease. GlcNAc-PT protein exists in the form of complex. The 偽 / 尾 subunit is encoded by GNPTAB gene, and 緯 subunit is encoded by GNPTAG gene. In this study, we collected a family of four generations of Chinese, four of whom suffered from mucoid storage. Linkage analysis showed that the pathogenicity gene of this strain was linked to the Marker D20S346 on chromosome 12. The reported pathogenicity gene GNPTAB is located at this location. By sequencing the GNPTAB, a heterozygous mutation was found in this pedigree, one was a reported shearing mutation IVS13 1GA(C.2715 GAA, and the other was a newly discovered nonsense mutation, p. R364XC1090CTA. All four patients in this family have these two mutations. The mutation was also not found in other healthy individuals in this family compared with 226 healthy controls. According to previous reports, IVS13 1GA(c.2715 1GA) caused the gene to skip the 1103bp base of exon 13 during transcription, leading to splicing directly from exon 12 to exon 14. The newly discovered pointless mutation p.R364XC1090CT) truncated the 偽 subunit of GNPTAB gene, resulting in a truncated 偽 subunit encoding protein and a complete loss of 尾 subunit coding protein. This study is the first reported heterozygous mutation of GNPTAB gene leading to ML 鈪，

本文編號(hào)：1849165