[
Mol Reprod Dev,
2017]
Silencing by RNA interference, triggered using double-stranded RNA (dsRNA), is transmitted from parent to progeny in some animals. We examined the mechanism of this inheritance by delivering fluorescent dsRNA (magenta) into the body cavity of the worm Caenorhabditis elegans. The fluorescent dsRNA permeates interstitial spaces between cells, and can be seen within invaginations of the syncytial germ line and between sperm within the spermatheca. This article is protected by copyright. All rights reserved.
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Am J Med Genet A,
2020]
The heterozygous deletion of 15q13.3 is a recurrently observed microdeletion syndrome associated with a relatively mild phenotype including learning disability and language impairment. In contrast, the homozygous deletion of 15q13.3 is extremely rare and is associated with a much severer phenotype that includes epileptic encephalopathy, profound intellectual disability, and hypotonia. Which of the genes within the deleted interval is responsible for the more severe features when biallelically deleted is currently unknown. Here, we report a patient with profound hypotonia, severe intellectual disability, and seizures who had biallelic loss-of-function variants in OTUD7A: a 15q13.3 deletion including the OTUD7A locus, and a frameshift OTUD7A variant c.1125del, p.(Glu375Aspfs*11). Unexpectedly, both aberrations occurred de novo. Our experiment using Caenorhabditis elegans showed that worms carrying a corresponding homozygous variant in the homolog OTUB-2 exhibited weakened muscle contraction suggestive of aberrant neuromuscular transmission. We concluded that the biallelic complete loss of OTUD7A in humans represents a presumably new autosomal recessive disorder characterized by profound hypotonia, severe intellectual disability, and seizures.