Phenotypic and molecular spectra of patients with switch/sucrose nonfermenting complex-related intellectual disability disorders in Korea.
BMC Med Genomics
; 14(1): 254, 2021 10 27.
Article
em En
| MEDLINE
| ID: mdl-34706719
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Anormalidades Múltiplas
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Deformidades Congênitas do Pé
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Deformidades Congênitas da Mão
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Face
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Hipotricose
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Deficiência Intelectual
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Micrognatismo
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Pescoço
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Infant
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Male
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Newborn
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article