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 metadata

https://www.hal.inserm.fr/inserm-03133278
Contributor : Catalina Betancur Connect in order to contact the contributor
Submitted on : Friday, February 5, 2021 - 7:54:19 PM
Last modification on : Sunday, June 26, 2022 - 9:39:12 AM
Long-term archiving on: : Friday, May 7, 2021 - 8:29:08 AM

File

Betancur review gene constrain...
Files produced by the author(s)

Identifiers

Citation

Catalina Betancur, Joseph D 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

71

Files downloads

246