Skip to Main content Skip to Navigation
Journal articles

Gene constraint and genotype–phenotype correlations in neurodevelopmental disorders

Abstract : With the advent and widespread adoption of high-throughput DNA sequencing, genetic discoveries in neurodevelopmental disorders (NDDs) are advancing very rapidly. The identification of novel NDD genes and of rare, highly penetrant pathogenic variants is leading to improved understanding of genotypephenotype correlations. Here we emphasize the importance of large-scale, reference databases such as gnomAD to determine gene and variant level constraints and facilitate gene discovery, variant interpretation, and genotype-phenotype correlations. While the majority of dominant NDD genes are highly intolerant to variation, some apparent exceptions in reference databases are related to the presence of variants in transcripts that are not brain expressed and/or genes that show acquired somatic mosaicism in blood. Multiple NDD genes are being identified where varying phenotypes depend on the mode of inheritance (e.g., dominant or recessive), the nature (e.g., missense or truncating), or location of the mutation. Ongoing genome-wide analyses and targeted functional studies provide enhancements to the annotation of genes, gene products and variants, which will continue to facilitate gene and variant discovery and variant interpretation.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-03133278
Contributor : Catalina Betancur <>
Submitted on : Friday, February 5, 2021 - 7:54:19 PM
Last modification on : Wednesday, February 10, 2021 - 3:34:03 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2021-05-01

Please log in to resquest access to the document

Identifiers

Citation

Catalina Betancur, Joseph Buxbaum. Gene constraint and genotype–phenotype correlations in neurodevelopmental disorders. Current Opinion in Genetics and Development, Elsevier, 2020, 65, pp.69-75. ⟨10.1016/j.gde.2020.05.036⟩. ⟨inserm-03133278⟩

Share

Metrics

Record views

38