Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders.
Gene
; 706: 162-171, 2019 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-31085274
ABSTRACT
In clinical genetics, the need to discriminate between benign and pathogenic variants identified in patients with neurodevelopmental disorders is an absolute necessity. Copy number variants (CNVs) of small size can enable the identification of genes that are critical for neurologic development. However, assigning a definite association with a specific disorder is a difficult task. Among 328 trios analyzed over seven years of activity in a single laboratory, we identified 19 unrelated patients (5.8%) who carried a small (<500â¯kb) de novo CNV. Four patients had an additional independent de novo CNV. Nine had a variant that could be assigned as definitely pathogenic, whereas the remaining CNVs were considered as variants of unknown significance (VUS). We report clinical and molecular findings of patients harboring VUS. We reviewed the medical literature available for genes impacted by CNVs, obtained the probability of truncating loss-of-function intolerance, and compared overlapping CNVs reported in databases. The classification of small non-recurrent CNVs remains difficult but, among our findings, we provide support for a role of SND1 in the susceptibility of autism, describe a new case of the rare 17p13.1 microduplication syndrome, and report an X-linked duplication involving KIF4A and DLG3 as a likely cause of epilepsy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variações do Número de Cópias de DNA
/
Transtornos do Neurodesenvolvimento
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
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Male
Idioma:
En
Revista:
Gene
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália