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Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
The elephant in the shROOM: Evidence for
SHROO ...
The elephant in the shROOM: Evidence for
SHROOM4
in disease remains limited and conflicting
Back to course
Pdf Summary
The document explores the role of the SHROOM4 gene in neurodevelopmental disorders (NDD). Initially, SHROOM4 was identified as a cause of Stocco dos Santos X-linked intellectual developmental disorder (SDSX) in four affected male cousins. Since then, various SHROOM4 variants have been reported, but their pathogenicity and association with NDD remain uncertain. Recent studies have described different SHROOM4 variants in individuals with epilepsy, infantile spasms, or isolated pulmonary valve stenosis. However, the evidence for these variants causing NDD is disputed, and some variants may have a gain-of-function effect rather than a loss-of-function effect. Overall, there have been 24 SHROOM4 variants reported, with 17 having uncertain evidence for NDD association and seven having disputed evidence. The clinical features observed in individuals with SHROOM4 variants include neurodevelopmental disorders, epilepsy, and congenital anomalies/facial dysmorphisms. However, there is no apparent genotype-phenotype correlation, and functional analyses are needed to better understand the role of SHROOM4 in NDD. The study identified ten individuals with SHROOM4 sequence variants of uncertain clinical significance. These variants were inherited from the mother and localized to exons 4 or 6 of the gene. The document concludes that more research and functional analyses are necessary to determine the association between SHROOM4 variants and NDD and to understand the contribution of SHROOM4 to neurodevelopment.
Asset Subtitle
Co-Author - Jullianne Diaz, MS, CGC; Co-Author - Megan Martin, MS, CGC; Presenting Author - Najla Al-Sweel, PhD, DABMGG;
Meta Tag
Clinical History
Delineation of Diseases
Identification of Disease Genes
Intellectual disability
X-Inactivation/X-Linked Disease
Co-Author
Jullianne Diaz, MS, CGC
Co-Author
Megan Martin, MS, CGC
Presenting Author
Najla Al-Sweel, PhD, DABMGG
Keywords
SHROOM4 gene
neurodevelopmental disorders
SHROOM4 variants
epilepsy
infantile spasms
pulmonary valve stenosis
gain-of-function effect
loss-of-function effect
uncertain evidence
functional analyses
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