Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family.
We report the genetic analysis of autosomal dominant, nonsyndromic, progressive sensorineural hearing loss in a Chinese family. Using whole exome sequencing, we identified a missense variant (c.130C>T, p.R44C) in the MCM2 gene, which has a pro-apoptosis effect and is involved in the initiation of...
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| Format: | Article |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4510057?pdf=render |
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| author | Juanjuan Gao Qi Wang Cheng Dong Siqi Chen Yu Qi Yuhe Liu |
| author_facet | Juanjuan Gao Qi Wang Cheng Dong Siqi Chen Yu Qi Yuhe Liu |
| author_sort | Juanjuan Gao |
| collection | DOAJ |
| description | We report the genetic analysis of autosomal dominant, nonsyndromic, progressive sensorineural hearing loss in a Chinese family. Using whole exome sequencing, we identified a missense variant (c.130C>T, p.R44C) in the MCM2 gene, which has a pro-apoptosis effect and is involved in the initiation of eukaryotic genome replication. This missense variant is very likely to be the disease causing variant. It segregated with hearing loss in this pedigree, and was not found in the dbSNP database or databases of genomes and SNP in the Chinese population, in 76 patients with sporadic hearing loss, or in 145 normal individuals. We performed western blot and immunofluorescence to test the MCM2 protein expression in the cochlea of rats and guinea pigs, demonstrating that MCM2 was widely expressed in the cochlea and was also surprisingly expressed in the cytoplasm of terminally differentiated hair cells. We then transiently expressed the variant MCM2 cDNA in HEK293 cells, and found that these cells displayed a slight increase in apoptosis without any changes in proliferation or cell cycle, supporting the view that this variant is pathogenic. In summary, we have identified MCM2 as a novel gene responsible for nonsyndromic hearing loss of autosomal dominant inheritance in a Chinese family. |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:59:20Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-d9e10a8e0c8f47acb6bad68811cee6a52022-12-21T23:51:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013352210.1371/journal.pone.0133522Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family.Juanjuan GaoQi WangCheng DongSiqi ChenYu QiYuhe LiuWe report the genetic analysis of autosomal dominant, nonsyndromic, progressive sensorineural hearing loss in a Chinese family. Using whole exome sequencing, we identified a missense variant (c.130C>T, p.R44C) in the MCM2 gene, which has a pro-apoptosis effect and is involved in the initiation of eukaryotic genome replication. This missense variant is very likely to be the disease causing variant. It segregated with hearing loss in this pedigree, and was not found in the dbSNP database or databases of genomes and SNP in the Chinese population, in 76 patients with sporadic hearing loss, or in 145 normal individuals. We performed western blot and immunofluorescence to test the MCM2 protein expression in the cochlea of rats and guinea pigs, demonstrating that MCM2 was widely expressed in the cochlea and was also surprisingly expressed in the cytoplasm of terminally differentiated hair cells. We then transiently expressed the variant MCM2 cDNA in HEK293 cells, and found that these cells displayed a slight increase in apoptosis without any changes in proliferation or cell cycle, supporting the view that this variant is pathogenic. In summary, we have identified MCM2 as a novel gene responsible for nonsyndromic hearing loss of autosomal dominant inheritance in a Chinese family.http://europepmc.org/articles/PMC4510057?pdf=render |
| spellingShingle | Juanjuan Gao Qi Wang Cheng Dong Siqi Chen Yu Qi Yuhe Liu Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. PLoS ONE |
| title | Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. |
| title_full | Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. |
| title_fullStr | Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. |
| title_full_unstemmed | Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. |
| title_short | Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal Dominant Nonsyndromic Deafness in a Chinese Family. |
| title_sort | whole exome sequencing identified mcm2 as a novel causative gene for autosomal dominant nonsyndromic deafness in a chinese family |
| url | http://europepmc.org/articles/PMC4510057?pdf=render |
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