Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease
Abstract Aims This study aimed to identify a novel splicing‐altering LAMP2 variant associated with Danon disease. Methods and results To identify the potential genetic mutation in a Chinese pedigree, whole‐exome sequencing was conducted in the proband, and Sanger sequencing was performed on the prob...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.14417 |
| _version_ | 1797770737756405760 |
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| author | Di Fu Shuai Wang Yonghong Luo Sha Wu Daoquan Peng |
| author_facet | Di Fu Shuai Wang Yonghong Luo Sha Wu Daoquan Peng |
| author_sort | Di Fu |
| collection | DOAJ |
| description | Abstract Aims This study aimed to identify a novel splicing‐altering LAMP2 variant associated with Danon disease. Methods and results To identify the potential genetic mutation in a Chinese pedigree, whole‐exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice‐site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice‐site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality. Conclusions A novel splice‐site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease. |
| first_indexed | 2024-03-12T21:26:31Z |
| format | Article |
| id | doaj.art-607fff5fdbb348af84e9d99065cb341b |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-03-12T21:26:31Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-607fff5fdbb348af84e9d99065cb341b2023-07-28T06:30:48ZengWileyESC Heart Failure2055-58222023-08-011042479248610.1002/ehf2.14417Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon diseaseDi Fu0Shuai Wang1Yonghong Luo2Sha Wu3Daoquan Peng4Department of Cardiovascular Medicine The Second Xiangya Hospital, Central South University 410011 Hunan Changsha No. 139 Middle Renmin Road ChinaDepartment of Cardiovascular Medicine The Second Xiangya Hospital, Central South University 410011 Hunan Changsha No. 139 Middle Renmin Road ChinaDepartment of Cardiovascular Medicine The Second Xiangya Hospital, Central South University 410011 Hunan Changsha No. 139 Middle Renmin Road ChinaDepartment of Cardiovascular Medicine The Second Xiangya Hospital, Central South University 410011 Hunan Changsha No. 139 Middle Renmin Road ChinaDepartment of Cardiovascular Medicine The Second Xiangya Hospital, Central South University 410011 Hunan Changsha No. 139 Middle Renmin Road ChinaAbstract Aims This study aimed to identify a novel splicing‐altering LAMP2 variant associated with Danon disease. Methods and results To identify the potential genetic mutation in a Chinese pedigree, whole‐exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice‐site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice‐site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality. Conclusions A novel splice‐site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease.https://doi.org/10.1002/ehf2.14417Danon diseaseLAMP2Splicing mutationGenetic diagnosisMinigene assay |
| spellingShingle | Di Fu Shuai Wang Yonghong Luo Sha Wu Daoquan Peng Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease ESC Heart Failure Danon disease LAMP2 Splicing mutation Genetic diagnosis Minigene assay |
| title | Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease |
| title_full | Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease |
| title_fullStr | Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease |
| title_full_unstemmed | Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease |
| title_short | Identification of a novel splicing‐altering LAMP2 variant in a Chinese family with Danon disease |
| title_sort | identification of a novel splicing altering lamp2 variant in a chinese family with danon disease |
| topic | Danon disease LAMP2 Splicing mutation Genetic diagnosis Minigene assay |
| url | https://doi.org/10.1002/ehf2.14417 |
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