Suzuki H et al. (2020) Am J Med Genet A "Biallelic loss of OTUD7A causes severe muscular hypotonia, intellectual disability, and seizures."

Takenouchi T, Inaba M, Suzuki H, Doi M, Kosaki K, Mizuno S, Uehara T, Yamada M

[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.

Alison M (2009) J Pathol "Stem cells in pathobiology and regenerative medicine."

Alison M

[J Pathol, 2009]

This issue of the Journal of Pathology contains 16 articles largely dealing with the role of tissue-specific adult stem cells in the pathogenesis of disease, notably cancer. These authoritative reviews begin by describing the current knowledge regarding the identity and molecular regulation of normal tissue-specific stem cells, before itemizing their role in the aetiology and progression of disease. Fundamental concepts regarding the stem cell niche have been gleaned from studies of germ line stem cells in Drosophila and Caenorhabditis elegans, and these are described in detail in this issue. Somatic cell reprogramming, a process underlying not only therapeutic cloning but also the production of induced pluripotent stem (iPS) cells, is further discussed. Much attention is given to embryonic stem (ES) and iPS cells within the scientific community; this issue of the Journal of Pathology redresses this imbalance by illustrating the pivotal role of adult stem cells in much of human disease. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.