Congenital heart defects and left ventricular non-compaction in males with loss-of-function variants in NONO.
J Med Genet
; 54(1): 47-53, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27550220
ABSTRACT
BACKGROUND:
The non-POU domain containing octamer-binding gene (NONO) is located on chromosome Xq13.1 and encodes a member of a small family of RNA-binding and DNA-binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Loss-of-function variants in NONO have been described as a cause of intellectual disability in males but have not been described in association with congenital heart defects or cardiomyopathy. In this article, we seek to further define the phenotypic consequences of NONO depletion in human subjects.METHODS:
We searched a clinical database of over 6000 individuals referred for exome sequencing and over 60â 000 individuals referred for CNV analysis.RESULTS:
We identified two males with atrial and ventricular septal defects, left ventricular non-compaction (LVNC), developmental delay and intellectual disability, who harboured de novo, loss-of-function variants in NONO. We also identified a male infant with developmental delay, congenital brain anomalies and severe LVNC requiring cardiac transplantation, who inherited a single-gene deletion of NONO from his asymptomatic mother.CONCLUSIONS:
We conclude that in addition to global developmental delay and intellectual disability, males with loss-of-function variants in NONO may also be predisposed to developing congenital heart defects and LVNC with the penetrance of these cardiac-related problems being influenced by genetic, epigenetic, environmental or stochastic factors. Brain imaging of males with NONO deficiency may reveal structural defects with abnormalities of the corpus callosum being the most common. Although dysmorphic features vary between affected individuals, relative macrocephaly is a common feature.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
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Proteínas Associadas à Matriz Nuclear
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Fatores de Transcrição de Octâmero
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Cardiopatias Congênitas
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Ventrículos do Coração
Tipo de estudo:
Prognostic_studies
Limite:
Child
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Child, preschool
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article