The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss
Mutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies...
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| Format: | Article |
| Language: | English |
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The Royal Society
2014-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140107 |
| _version_ | 1818301659992817664 |
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| author | Tae-Jun Kwon Se-Kyung Oh Hong-Joon Park Osamu Sato Hanka Venselaar Soo Young Choi SungHee Kim Kyu-Yup Lee Jinwoong Bok Sang-Heun Lee Gert Vriend Mitsuo Ikebe Un-Kyung Kim Jae Young Choi |
| author_facet | Tae-Jun Kwon Se-Kyung Oh Hong-Joon Park Osamu Sato Hanka Venselaar Soo Young Choi SungHee Kim Kyu-Yup Lee Jinwoong Bok Sang-Heun Lee Gert Vriend Mitsuo Ikebe Un-Kyung Kim Jae Young Choi |
| author_sort | Tae-Jun Kwon |
| collection | DOAJ |
| description | Mutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies have been performed on the previously reported myosin mutations. We performed screening and functional studies for mutations in the MYO1A and MYO6 genes in Korean cases of autosomal dominant non-syndromic HL. We identified four novel heterozygous mutations in MYO6. Three mutations (p.R825X, p.R991X and Q918fsX941) produce a premature truncation of the myosin VI protein. Another mutation, p.R205Q, was associated with diminished actin-activated ATPase activity and actin gliding velocity of myosin VI in an in vitro analysis. This finding is consistent with the results of protein modelling studies and corroborates the pathogenicity of this mutation in the MYO6 gene. One missense variant, p.R544W, was found in the MYO1A gene, and in silico analysis suggested that this variant has deleterious effects on protein function. This finding is consistent with the results of protein modelling studies and corroborates the pathogenic effect of this mutation in the MYO6 gene. |
| first_indexed | 2024-12-13T05:26:32Z |
| format | Article |
| id | doaj.art-145dba04990f4e779e878c8183f3065a |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-13T05:26:32Z |
| publishDate | 2014-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-145dba04990f4e779e878c8183f3065a2022-12-21T23:58:10ZengThe Royal SocietyOpen Biology2046-24412014-01-014710.1098/rsob.140107140107The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing lossTae-Jun KwonSe-Kyung OhHong-Joon ParkOsamu SatoHanka VenselaarSoo Young ChoiSungHee KimKyu-Yup LeeJinwoong BokSang-Heun LeeGert VriendMitsuo IkebeUn-Kyung KimJae Young ChoiMutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies have been performed on the previously reported myosin mutations. We performed screening and functional studies for mutations in the MYO1A and MYO6 genes in Korean cases of autosomal dominant non-syndromic HL. We identified four novel heterozygous mutations in MYO6. Three mutations (p.R825X, p.R991X and Q918fsX941) produce a premature truncation of the myosin VI protein. Another mutation, p.R205Q, was associated with diminished actin-activated ATPase activity and actin gliding velocity of myosin VI in an in vitro analysis. This finding is consistent with the results of protein modelling studies and corroborates the pathogenicity of this mutation in the MYO6 gene. One missense variant, p.R544W, was found in the MYO1A gene, and in silico analysis suggested that this variant has deleterious effects on protein function. This finding is consistent with the results of protein modelling studies and corroborates the pathogenic effect of this mutation in the MYO6 gene.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140107myosinmutationatpaseprotein structuregene |
| spellingShingle | Tae-Jun Kwon Se-Kyung Oh Hong-Joon Park Osamu Sato Hanka Venselaar Soo Young Choi SungHee Kim Kyu-Yup Lee Jinwoong Bok Sang-Heun Lee Gert Vriend Mitsuo Ikebe Un-Kyung Kim Jae Young Choi The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss Open Biology myosin mutation atpase protein structure gene |
| title | The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss |
| title_full | The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss |
| title_fullStr | The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss |
| title_full_unstemmed | The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss |
| title_short | The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss |
| title_sort | effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non syndromic hearing loss |
| topic | myosin mutation atpase protein structure gene |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140107 |
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