Analysis of the heteroplasmy level and transmitted features in hearing-loss pedigrees with mitochondrial 12S rRNA A1555G mutation.
Analysis of the heteroplasmy level and transmitted features in hearing-loss pedigrees with mitochondrial 12S rRNA A1555G mutation.
复制标题
线粒体12S rRNA A1555G突变听力损失家系的异质性水平和传播特征分析。
DOI：
10.1186/1471-2156-15-26
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发表时间：
2014-02-17
期刊：
影响因子：
2.9
通讯作者：
Dai P
中科院分区：
文献类型：
--
作者：
Zhu Y;Huang S;Kang D;Han M;Wang G;Yuan Y;Su Y;Yuan H;Zhai S;Dai P
BackgroundMitochondrial cytopathies are characterized by a large variability of clinical phenotypes and severity. The amount of mutant mitochondrial DNA (mtDNA) in a cell, called the heteroplasmy level, is an important determinant of the degree of mitochondrial dysfunction and therefore disease severity. Understanding the distribution of heteroplasmy levels across a group of offspring is an important step in understanding the inheritance of diseases. Recently, the mtDNA A1555G mutation was found to be associated with non-syndromic and drug-induced hearing loss.ResultsHere, we report five pedigrees with multiple members having the A1555G mutation and showing diverse clinical manifestations and different heteroplasmy levels. Clinical evaluations revealed that the hearing impairment phenotypes varied with respect to the severity of hearing loss, age of onset of hearing loss, and pattern of audiometric configuration. These five Chinese pedigrees had different penetrance of hearing loss, ranging from 10–52%. A molecular study showed that the average heteroplasmy rates of the five pedigrees were 31.98% (0–91.35%), 78.28% (32.8–96.08%), 87.99% (82.32–94.65%), 93.34% (91.02–95.05%), and 93.57% (91.38–94.24%). There was no gradual tendency of heteroplasmy to increase or decrease along with transmission. A study of the relationship between clinical features and genetic background found that the percentage of deafness was 0 when the heteroplasmy level was less than 50%, 25% when the heteroplasmy level was 50–80%, 47.06% when the heteroplasmy level was 80–90%, and 57.58% when the heteroplasmy level exceeded 90%. The risk of deafness rose with the heteroplasmy level.ConclusionsThe results suggest that there are large random shifts in the heteroplasmy level between mothers and offspring with the A1555G mutation; heteroplasmy could disappear randomly when the heteroplasmy level of the pedigree was low enough, and no regular pattern was found. The heteroplasmy level may be one of the factors influencing the penetrance of deafness caused by the mtDNA A1555G mutation.
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DOI：
10.1016/j.bbrc.2009.02.014
发表时间：
2009-04-03
影响因子：
3.1
作者：
Sousa de Moraes, Vanessa Cristine;Alexandrino, Fabiana;Sartorato, Edi Lucia
通讯作者：
Sartorato, Edi Lucia
影响因子：
--
作者：
Bai Y;Wang Z;Dai W;Li Q;Chen G;Cong N;Guan M;Li H
通讯作者：
Li H
一种快速检测与氨基糖苷类引起的耳聋相关的五种已知突变的方法。
影响因子：
--
作者：
Bardien, Soraya;Human, Hannique;Harris, Tashneem;Hefke, Gwynneth;Veikondis, Rene;Schaaf, H. Simon;van der Merwe, Lize;Greinwald, John H.;Fagan, Johan;de Jong, Greetje
通讯作者：
de Jong, Greetje
影响因子：
4.9
作者：
Qian, Yaping;Guan, Min-Xin
通讯作者：
Guan, Min-Xin
影响因子：
2
作者：
Young, Wie-Yen;Zhao, Lidong;Guan, Min-Xin
通讯作者：
Guan, Min-Xin