Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea
Abstract Background The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, in...
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BMC
2021-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-021-01104-9 |
| _version_ | 1819009370580582400 |
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| author | Yena Lee Yunha Choi Go Hun Seo Gu-Hwan Kim Changwon Keum Yoo-Mi Kim Hyo-Sang Do Jeongmin Choi In Hee Choi Han-Wook Yoo Beom Hee Lee |
| author_facet | Yena Lee Yunha Choi Go Hun Seo Gu-Hwan Kim Changwon Keum Yoo-Mi Kim Hyo-Sang Do Jeongmin Choi In Hee Choi Han-Wook Yoo Beom Hee Lee |
| author_sort | Yena Lee |
| collection | DOAJ |
| description | Abstract Background The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin–Siris syndrome (CSS), Nicolaides–Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs). Methods Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed. Results ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12). Conclusions SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders. |
| first_indexed | 2024-12-21T00:55:18Z |
| format | Article |
| id | doaj.art-f92541cb745f4e59a75024cc2e7bab11 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-21T00:55:18Z |
| publishDate | 2021-10-01 |
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| series | BMC Medical Genomics |
| spelling | doaj.art-f92541cb745f4e59a75024cc2e7bab112022-12-21T19:21:19ZengBMCBMC Medical Genomics1755-87942021-10-0114111010.1186/s12920-021-01104-9Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in KoreaYena Lee0Yunha Choi1Go Hun Seo2Gu-Hwan Kim3Changwon Keum4Yoo-Mi Kim5Hyo-Sang Do6Jeongmin Choi7In Hee Choi8Han-Wook Yoo9Beom Hee Lee10Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine3Billion Inc.Medical Genetics Center, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine3Billion Inc.Department of Pediatrics, Chungnam National University Sejong Hospital, College of Medicine, Chungnam National UniversityGenome Research Center for Birth Defects and Genetic Diseases, Asan Institute for Life Sciences, Asan Medical CenterGenome Research Center for Birth Defects and Genetic Diseases, Asan Institute for Life Sciences, Asan Medical CenterDepartment of Genetic Counseling, University of Ulsan College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineDepartment of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of MedicineAbstract Background The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin–Siris syndrome (CSS), Nicolaides–Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs). Methods Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed. Results ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12). Conclusions SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders.https://doi.org/10.1186/s12920-021-01104-9Intellectual disabilityChromatin assembly and disassemblyLanguage development disordersCorpus callosumWhole-exome sequencingGermline mutation |
| spellingShingle | Yena Lee Yunha Choi Go Hun Seo Gu-Hwan Kim Changwon Keum Yoo-Mi Kim Hyo-Sang Do Jeongmin Choi In Hee Choi Han-Wook Yoo Beom Hee Lee Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea BMC Medical Genomics Intellectual disability Chromatin assembly and disassembly Language development disorders Corpus callosum Whole-exome sequencing Germline mutation |
| title | Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea |
| title_full | Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea |
| title_fullStr | Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea |
| title_full_unstemmed | Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea |
| title_short | Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea |
| title_sort | phenotypic and molecular spectra of patients with switch sucrose nonfermenting complex related intellectual disability disorders in korea |
| topic | Intellectual disability Chromatin assembly and disassembly Language development disorders Corpus callosum Whole-exome sequencing Germline mutation |
| url | https://doi.org/10.1186/s12920-021-01104-9 |
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