identified overlapping microduplications at Xp11.22, encompassing HUWE1 and HSD17B10 , ranging in size between 0.4 and 1 Mb [ 5 , 6 ]. Orivoli S, Pavlidis E, Cantalupo G, Pezzella M, Zara F, Garavelli L, Pisani F, Piccolo B. Neuropediatrics. Previously published variants are shown on the left and variants in the present cohort on the right. Within this region, only one gene, the HUWE1 gene, coding the E3 ubiquitin protein ligase, turned out to be duplicated in all previously described patients. In 12 families with mild to moderate non-syndromic XLID, Froyen et al. Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). “The paper is an important step in understanding how increased or decreased activity of HUWE1 can alter circuit function and lead to intellectual disability,” said TSRI Research Assistant Karla Opperman, first author of the study. In this review, we discuss how Huwe1 contributes to nervous system development, function and disease. Facial and limb features of individuals with. Or view hourly updated newsfeeds in your RSS reader: Keep up to date with the latest news from ScienceDaily via social networks: Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Despite extensive research, in half of XLID-patients, the responsible gene responsible has not yet been identified. The advent of next-generation sequencing has proven to be a key force in the identification of new genes associated with intellectual disability. Here you will find a list of rare diseases related to the HUWE1. "The fact that HUWE1 regulates the dose of several other proteins in the brains, has an important impact on the quest for new therapies. Although mutations in HUWE1 cause heterogenous neurodevelopmental X-linked intellectual disabilities (XLIDs), the disease mechanisms common to these syndromes remain unknown. Missense variants reported previously appear t … The study represents important progress in understanding the molecular underpinnings of intellectual disability. Guy Froyen, Stefanie Belet, Francisco Martinez, Cíntia Barros Santos-Rebouças, Matthias Declercq, Jelle Verbeeck, Lene Donckers, Siren Berland, Sonia Mayo, Monica Rosello, Márcia Mattos Gonçalves Pimentel, Natalia Fintelman-Rodrigues, Randi Hovland, Suely Rodrigues dos Santos, F. Lucy Raymond, Tulika Bose, Mark A. Corbett, Leslie Sheffield, Conny M.A. Clinical Features. HUWE1 encodes an ubiquitin protein ligase involved in various cellular processes, including synaptogenesis, associated to the Turner type X-linked syndromic cognitive disability (OMIM:309590) and ASD (Moortgat et al., 2018). In these females, the X inactivation pattern appeared skewed in favour of the affected transcript. Content on this website is for information only. Male patients are in blue and female in red. 2 to 3 % of the children are born with an intellectual disability that could be possibly by a genetic defect, but in 80% of these cases, we do not know - yet - which genes are responsible. He had severe intellectual disability (IQ less than 20), no speech, and notable dysmorphic features, including facial asymmetry, bifrontal narrowing with sunken midface, prominent brow, hypotelorism, upslanting palpebral fissures, prominent nose, long philtrum, and thin lips. Deciphering … It is not intended to provide medical or other professional advice. Intellectual disability (ID), once called mental retardation, is characterized by below-average intelligence or mental ability and a lack of skills necessary for day-to-day living. Pedigrees of families with maternally inherited HUWE1 variants. 2020 Dec 3;107(6):1157-1169. doi: 10.1016/j.ajhg.2020.10.005. Am J Hum Genet. Epub 2019 Feb 21. IDs. Absence of speech (or less than five words) Moderate to profound intellectual disability in many, mild intellectual disability in some. It would then be possible to intervene in these different proteins. ScienceDaily shares links with sites in the. Comparing the duplicated segments, a minimum region of overlap has been identified. 2021 Feb 26;49(1):365-377. doi: 10.1042/BST20200694. Mammals Evolved Big Brains After Big Disasters, New Perspective On Genomes of Archaic Humans, Genetic Defect Causing Intellectual Disability Found, Better Genetic Decoding of Neurodevelopmental Disorders, New Intellectual Disability Syndrome Caused by Genetic Damage to Single Gene, Three Reasons Why COVID-19 Can Cause Silent Hypoxia. Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/-catenin pathway in a Drosophila model for intellectual disability. See this image and copyright information in PMC. Palmer EE, Carroll R, Shaw M, Kumar R, Minoche AE, Leffler M, Murray L, Macintosh R, Wright D, Troedson C, McKenzie F, Townshend S, Ward M, Nawaz U, Ravine A, Runke CK, Thorland EC, Hummel M, Foulds N, Pichon O, Isidor B, Le Caignec C, Demeer B, Andrieux J, Albarazi SH, Bye A, Sachdev R, Kirk EP, Cowley MJ, Field M, Gecz J. The authors declare that they have no competing interests. Too much protein HUWE1 causes intellectual disability. Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Vandewalle J , et al. Study Explains Potential Causes for 'Happy Hypoxia' Condition in COVID-19 Patients, Fasting Lowers Blood Pressure by Reshaping the Gut Microbiota, Espresso, Latte or Decaf? 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