Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease
AIM: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations. METHODS: A Chinese STGD family and 200 normal controls were collected. Whole exome sequen...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Press of International Journal of Ophthalmology (IJO PRESS)
2020-04-01
|
| Series: | International Journal of Ophthalmology |
| Subjects: | |
| Online Access: | http://www.ijo.cn/en_publish/2020/4/20200422.pdf |
| _version_ | 1818291640421318656 |
|---|---|
| author | Xiao-Dan Hao Ying Liu Bao-Wei Li Wei Wu Xiao-Wen Zhao |
| author_facet | Xiao-Dan Hao Ying Liu Bao-Wei Li Wei Wu Xiao-Wen Zhao |
| author_sort | Xiao-Dan Hao |
| collection | DOAJ |
| description | AIM: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations.
METHODS: A Chinese STGD family and 200 normal controls were collected. Whole exome sequencing (WES) and bioinformatics analysis were performed to find the pathogenic gene mutation. Physico-chemical parameters of mutant and wildtype proteins were computed by ProtParam tool. Domains analysis was performed by SMART online software. HOPE online software was used to analyze the structural effects of mutation. Immunofluorescence, quantitative real-time polymerase chain reaction and Western blotting were used for expression analysis.
RESULTS: Using WES, a novel homozygous mutation (NM_000350: c.G3190C, p.G1064R) in ABCA4 gene was identified. This mutation showed co-segregation with phenotype in this family. It was not found in the 200 unrelated health controls and absent from any databases. It was considered “Deleterious” as predicted by five function prediction softwares, and was highly conserved during evolution. ABCA4 was expressed highly in the human eye and mouse retina. The p.G1064R was located in AAA domain, may force the local backbone into an incorrect conformation, disturb the local structure, and reduce the activity of ATPase resulting in the disease pathology.
CONCLUSION: We define a novel pathogenic mutation (c.G3190C of ABCA4) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations. |
| first_indexed | 2024-12-13T02:47:17Z |
| format | Article |
| id | doaj.art-ea48406c9a7f4fe2b64fa63f0bddf8fc |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-12-13T02:47:17Z |
| publishDate | 2020-04-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-ea48406c9a7f4fe2b64fa63f0bddf8fc2022-12-22T00:02:09ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982020-04-0113467167610.18240/ijo.2020.04.22Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt diseaseXiao-Dan Hao0Ying Liu1Bao-Wei Li2Wei Wu3Xiao-Wen Zhao4Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, Shandong Province, ChinaInstitute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, Shandong Province, ChinaInstitute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, Shandong Province, ChinaInstitute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, Shandong Province, ChinaState Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, ChinaAIM: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations. METHODS: A Chinese STGD family and 200 normal controls were collected. Whole exome sequencing (WES) and bioinformatics analysis were performed to find the pathogenic gene mutation. Physico-chemical parameters of mutant and wildtype proteins were computed by ProtParam tool. Domains analysis was performed by SMART online software. HOPE online software was used to analyze the structural effects of mutation. Immunofluorescence, quantitative real-time polymerase chain reaction and Western blotting were used for expression analysis. RESULTS: Using WES, a novel homozygous mutation (NM_000350: c.G3190C, p.G1064R) in ABCA4 gene was identified. This mutation showed co-segregation with phenotype in this family. It was not found in the 200 unrelated health controls and absent from any databases. It was considered “Deleterious” as predicted by five function prediction softwares, and was highly conserved during evolution. ABCA4 was expressed highly in the human eye and mouse retina. The p.G1064R was located in AAA domain, may force the local backbone into an incorrect conformation, disturb the local structure, and reduce the activity of ATPase resulting in the disease pathology. CONCLUSION: We define a novel pathogenic mutation (c.G3190C of ABCA4) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations.http://www.ijo.cn/en_publish/2020/4/20200422.pdfstargardt diseasewhole-exome sequencingabca4novel mutationretina |
| spellingShingle | Xiao-Dan Hao Ying Liu Bao-Wei Li Wei Wu Xiao-Wen Zhao Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease International Journal of Ophthalmology stargardt disease whole-exome sequencing abca4 novel mutation retina |
| title | Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease |
| title_full | Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease |
| title_fullStr | Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease |
| title_full_unstemmed | Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease |
| title_short | Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease |
| title_sort | exome sequencing analysis identifies novel homozygous mutation in abca4 in a chinese family with stargardt disease |
| topic | stargardt disease whole-exome sequencing abca4 novel mutation retina |
| url | http://www.ijo.cn/en_publish/2020/4/20200422.pdf |
| work_keys_str_mv | AT xiaodanhao exomesequencinganalysisidentifiesnovelhomozygousmutationinabca4inachinesefamilywithstargardtdisease AT yingliu exomesequencinganalysisidentifiesnovelhomozygousmutationinabca4inachinesefamilywithstargardtdisease AT baoweili exomesequencinganalysisidentifiesnovelhomozygousmutationinabca4inachinesefamilywithstargardtdisease AT weiwu exomesequencinganalysisidentifiesnovelhomozygousmutationinabca4inachinesefamilywithstargardtdisease AT xiaowenzhao exomesequencinganalysisidentifiesnovelhomozygousmutationinabca4inachinesefamilywithstargardtdisease |