|
1000
|
Abstract/Summary
|
-
<jats:title>Abstract</jats:title>
<jats:p>Neuron navigators (NAVs) are cytoskeleton-associated proteins well known for their role in axonal guidance, neuronal migration, and neurite growth necessary for neurodevelopment. Neuron navigator 3 (NAV3) is one of the three NAV proteins highly expressed in the embryonic and adult brain. However, the role of the <jats:italic>NAV3</jats:italic> gene in human disease is not well-studied. Recently, five bi-allelic and three mono-allelic variants in <jats:italic>NAV3</jats:italic> were reported in 12 individuals from eight unrelated families with neurodevelopmental disorder (NDD). Here, we report five patients from three unrelated consanguineous families segregating autosomal recessive NDD. Patients have symptoms of dysmorphism, intellectual disability, developmental delay, and behavioral abnormalities. Exome sequencing (ES) was performed on two affected individuals from one large family, and one affected individual from each of the other two families. ES revealed two homozygous nonsense c.6325C > T; p.(Gln2109Ter) and c.6577C > T; p.(Arg2193Ter) and a homozygous splice site (c.243 + 1G > T) variants in the <jats:italic>NAV3</jats:italic> (NM_001024383.2). Analysis of single-cell sequencing datasets from embryonic and young adult human brains revealed that <jats:italic>NAV3</jats:italic> is highly expressed in the excitatory neurons, inhibitory neurons, and microglia, consistent with its role in neurodevelopment. In conclusion, in this study, we further validate biallelic protein truncating variants in <jats:italic>NAV3</jats:italic> as a cause of NDD, expanding the spectrum of pathogenic variants in this newly discovered NDD gene.</jats:p>
|
|
1000
|
Hinweis
|
-
DeepGreen-ID: ecd4d8e7dd29461a8fa1e7eb42149561 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
|
