Phenotypic shift in copy number variants: Evidence in 16p11.2 duplication syndrome.
Genet Med
; 25(1): 151-154, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36609147
ABSTRACT
PURPOSE:
Recurrent 16p11.2 duplications produce a wide range of clinical outcomes with varying effects on cognition and social functioning. Family-based studies of copy number variants (CNVs) have revealed significant contributions of genomic background on variable expressivity. In this study, we measured the phenotypic effect of 16p11.2 duplications and quantified the modulating effect of familial background on cognitive and social outcomes.METHODS:
Genomic and clinical data were ascertained from 41 probands with a 16p11.2 duplication and their first-degree relatives. Paired comparisons were completed to determine the duplication's effect on expected vs actual performance on standardized tests of intelligence (IQ) and social functioning (Social Responsiveness Scale-2). Intraclass correlations between relatives and probands were also calculated.RESULTS:
Cognitive and social functioning were significantly lower among individuals with 16p11.2 duplications than their CNV-negative relatives, whereas intraclass correlations between the groups remained high for full-scale IQ and Social Responsiveness Scale-2 scores.CONCLUSION:
The 16p11.2 duplication confers deleterious effects on cognition and social functioning, whereas familial background significantly influences phenotypic expression of these traits. Understanding variable expressivity in CNV disorders has implications for anticipatory clinical care, particularly for individuals who receive a genetic diagnosis at an early age, long before the full scope of manifestations becomes evident.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
Problema de salud:
1_geracao_evidencia_conhecimento
Asunto principal:
Deleción Cromosómica
/
Variaciones en el Número de Copia de ADN
Límite:
Humans
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article