Please wait, while we are loading the content...
| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Li, Ming Lin, Jingqi Fei, Hongjun Liu, Jinyu Chen, Yiyao Han, Xu Wang, Yanlin Wang, Jian Hua, Renyi Li, Shuyuan Li, Niu |
| Abstract | Background To determine the pathogenicity of a novel splicing variant in the SMARCC2 gene identified from a pair of adult male monozygotic twins with neurodevelopmental disorder, and to investigate the genotype-phenotype characteristics associated with SMARCC2 variants. Methods Whole-exome sequencing (WES) was conducted on the proband, and candidate variants were validated using Sanger sequencing within the family. The effect of the identified splicing variant on SMARCC2 mRNA processing was analyzed using reverse transcription PCR (RT-PCR) and TA-clone sequencing using samples derived from the proband. The clinical features of the twins were collected and compared with the previously reported patients. Results The twin adult males displayed comparable phenotypes, characterized by moderate developmental delay, intellectual and language delays, dense hair, craniofacial anomalies, scoliosis, cryptorchidism, hypotonia, behavioral abnormalities, allergic purpura and eczema, and drug allergies. WES unveiled a previously unreported heterozygous splice variant of the SMARCC2 gene (NM_003075.3: c.1496 + 1G > T). Sanger sequencing confirmed that the variant was de novo in both patients. TA-clone sequencing of the RT-PCR fragments showed that the canonical splicing variant resulted in two distinct aberrant splicing events in SMARCC2 mRNA. Specifically, approximately 80% of the mutant clones resulted from the in-frame insertion of 126 bases in intron 16, while the remaining 20% showed an in-frame deletion of exon 16 (c.1383_1496del). Crystal structure analysis showed that both in-frame alterations hindered the proper formation of the alpha helix structure within the SMARCC2 protein. An analysis of genotype-phenotype correlations indicated that our patients displayed neurological phenotypes of greater severity than those observed in patients with truncating variants, instead aligning more closely with the characteristics of the missense/in-frame variant group. Conclusion We identified and reported a pair of twins suffering from syndromic neurodevelopmental disorders caused by a novel splicing variant of SMARCC2. Our findings further reinforce the notion that individuals harboring missense/in-frame variants in SMARCC2 are prone to experiencing more severe neurological phenotypes. |
| Related Links | https://ojrd.biomedcentral.com/counter/pdf/10.1186/s13023-024-03510-5.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17501172 |
| DOI | 10.1186/s13023-024-03510-5 |
| Journal | Orphanet Journal of Rare Diseases |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-02-03 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Pharmacology Toxicology Human Genetics SMARCC2 Syndromic neurodevelopmental disorder Novel splicing variant cDNA sequencing Crystal structure analysis Medicine/Public Health Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology (medical) Genetics (clinical) |
| Journal Impact Factor | 3.4/2023 |
| 5-Year Journal Impact Factor | 3.9/2023 |
National Digital Library of India (NDLI) is a virtual repository of learning resources which is not just a repository with search/browse facilities but provides a host of services for the learner community. It is sponsored and mentored by Ministry of Education, Government of India, through its National Mission on Education through Information and Communication Technology (NMEICT). Filtered and federated searching is employed to facilitate focused searching so that learners can find the right resource with least effort and in minimum time. NDLI provides user group-specific services such as Examination Preparatory for School and College students and job aspirants. Services for Researchers and general learners are also provided. NDLI is designed to hold content of any language and provides interface support for 10 most widely used Indian languages. It is built to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is designed to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is developed, operated and maintained from Indian Institute of Technology Kharagpur.
Learn more about this project from here.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Education, through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
| Sl. | Authority | Responsibilities | Communication Details |
|---|---|---|---|
| 1 | Ministry of Education (GoI), Department of Higher Education |
Sanctioning Authority | https://www.education.gov.in/ict-initiatives |
| 2 | Indian Institute of Technology Kharagpur | Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project | https://www.iitkgp.ac.in |
| 3 | National Digital Library of India Office, Indian Institute of Technology Kharagpur | The administrative and infrastructural headquarters of the project | Dr. B. Sutradhar bsutra@ndl.gov.in |
| 4 | Project PI / Joint PI | Principal Investigator and Joint Principal Investigators of the project |
Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon |
| 5 | Website/Portal (Helpdesk) | Queries regarding NDLI and its services | support@ndl.gov.in |
| 6 | Contents and Copyright Issues | Queries related to content curation and copyright issues | content@ndl.gov.in |
| 7 | National Digital Library of India Club (NDLI Club) | Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach | clubsupport@ndl.gov.in |
| 8 | Digital Preservation Centre (DPC) | Assistance with digitizing and archiving copyright-free printed books | dpc@ndl.gov.in |
| 9 | IDR Setup or Support | Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops | idr@ndl.gov.in |
|
Loading...
|