A novel non-sense variant in the OFD1 gene caused Joubert syndrome
Background: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis.Methods: Whole...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1064762/full |
| _version_ | 1828067778875097088 |
|---|---|
| author | Chen Li Xingwang Wang Fake Li Hongke Ding Ling Liu Ying Xiong Chaoxiang Yang Yan Zhang Jing Wu Aihua Yin |
| author_facet | Chen Li Xingwang Wang Fake Li Hongke Ding Ling Liu Ying Xiong Chaoxiang Yang Yan Zhang Jing Wu Aihua Yin |
| author_sort | Chen Li |
| collection | DOAJ |
| description | Background: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis.Methods: Whole-exome sequencing and Sanger sequencing were performed to screen the causative gene variants in a suspected JBS family. RNA-seq and protein model prediction were performed to clarify the potential pathogenic mechanism. A more comprehensive review of previously reported cases with OFD1 variants is presented and may help to establish a genotype–phenotype.Results: We identified a novel non-sense variant in the OFD1 gene, OFD1 (NM_003611.3): c.2848A>T (p.Lys950Ter). Sanger sequencing confirmed cosegregation among this family. RNA-seq confirmed that partial degradation of mutant transcripts, which was predicted to be caused by the non-sense-mediated mRNA decay (NMD) mechanism, may explain the reduction in the proportion of mutant transcripts. Protein structure prediction of the non-sense variant transcript revealed that this variant may lead to a change in the OFD1 protein structure.Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease. |
| first_indexed | 2024-04-10T23:50:51Z |
| format | Article |
| id | doaj.art-fbdc34e20395483a8f13db3ecd0350dd |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T23:50:51Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-fbdc34e20395483a8f13db3ecd0350dd2023-01-10T19:02:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10647621064762A novel non-sense variant in the OFD1 gene caused Joubert syndromeChen Li0Xingwang Wang1Fake Li2Hongke Ding3Ling Liu4Ying Xiong5Chaoxiang Yang6Yan Zhang7Jing Wu8Aihua Yin9Medical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Imaging Department, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaMedical Genetic Center, Guangdong Women and Children Hospital, Guangzhou, ChinaBackground: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis.Methods: Whole-exome sequencing and Sanger sequencing were performed to screen the causative gene variants in a suspected JBS family. RNA-seq and protein model prediction were performed to clarify the potential pathogenic mechanism. A more comprehensive review of previously reported cases with OFD1 variants is presented and may help to establish a genotype–phenotype.Results: We identified a novel non-sense variant in the OFD1 gene, OFD1 (NM_003611.3): c.2848A>T (p.Lys950Ter). Sanger sequencing confirmed cosegregation among this family. RNA-seq confirmed that partial degradation of mutant transcripts, which was predicted to be caused by the non-sense-mediated mRNA decay (NMD) mechanism, may explain the reduction in the proportion of mutant transcripts. Protein structure prediction of the non-sense variant transcript revealed that this variant may lead to a change in the OFD1 protein structure.Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease.https://www.frontiersin.org/articles/10.3389/fgene.2022.1064762/fullJoubert syndromeOFD1novel non-sense variantMRIwhole exome sequencing (WES)RNA-seq |
| spellingShingle | Chen Li Xingwang Wang Fake Li Hongke Ding Ling Liu Ying Xiong Chaoxiang Yang Yan Zhang Jing Wu Aihua Yin A novel non-sense variant in the OFD1 gene caused Joubert syndrome Frontiers in Genetics Joubert syndrome OFD1 novel non-sense variant MRI whole exome sequencing (WES) RNA-seq |
| title | A novel non-sense variant in the OFD1 gene caused Joubert syndrome |
| title_full | A novel non-sense variant in the OFD1 gene caused Joubert syndrome |
| title_fullStr | A novel non-sense variant in the OFD1 gene caused Joubert syndrome |
| title_full_unstemmed | A novel non-sense variant in the OFD1 gene caused Joubert syndrome |
| title_short | A novel non-sense variant in the OFD1 gene caused Joubert syndrome |
| title_sort | novel non sense variant in the ofd1 gene caused joubert syndrome |
| topic | Joubert syndrome OFD1 novel non-sense variant MRI whole exome sequencing (WES) RNA-seq |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1064762/full |
| work_keys_str_mv | AT chenli anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT xingwangwang anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT fakeli anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT hongkeding anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT lingliu anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT yingxiong anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT chaoxiangyang anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT yanzhang anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT jingwu anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT aihuayin anovelnonsensevariantintheofd1genecausedjoubertsyndrome AT chenli novelnonsensevariantintheofd1genecausedjoubertsyndrome AT xingwangwang novelnonsensevariantintheofd1genecausedjoubertsyndrome AT fakeli novelnonsensevariantintheofd1genecausedjoubertsyndrome AT hongkeding novelnonsensevariantintheofd1genecausedjoubertsyndrome AT lingliu novelnonsensevariantintheofd1genecausedjoubertsyndrome AT yingxiong novelnonsensevariantintheofd1genecausedjoubertsyndrome AT chaoxiangyang novelnonsensevariantintheofd1genecausedjoubertsyndrome AT yanzhang novelnonsensevariantintheofd1genecausedjoubertsyndrome AT jingwu novelnonsensevariantintheofd1genecausedjoubertsyndrome AT aihuayin novelnonsensevariantintheofd1genecausedjoubertsyndrome |