Expanding the phenotypic spectrum associated with OPHN1 mutations: Report of 17 individuals with intellectual disability but no cerebellar hypoplasia. Missense variants reported previously appear t … 2020 Dec 3;107(6):1157-1169. doi: 10.1016/j.ajhg.2020.10.005. Although mutations in HUWE1 cause heterogenous neurodevelopmental X-linked intellectual disabilities (XLIDs), the disease mechanisms common to these syndromes remain unknown. Number in parenthesis indicates recurrent variants describing number of families reported for the variant. Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome. Intellectual disability can be due to external factors such as lack of oxygen at birth or to defects in the genetic material. Alterations in the genome integrity and accumulation of mutations have been tightly associated with the onset of neurodevelopmental disorders. Cerminara M, Spirito G, Pisciotta L, Squillario M, Servetti M, Divizia MT, Lerone M, Berloco B, Boeri S, Nobili L, Vozzi D, Sanges R, Gustincich S, Puliti A. Prevention and treatment information (HHS). (2008) identified mutations in the HUWE1 gene (300697.0001-300697.0003).There was some phenotypic variability between the families: one had associated macrocephaly, whereas the others had mild and profound mental retardation, respectively. Vandewalle J , et al. 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. The association of HUWE1 variants or rearrangements with X-linked intellectual disability (XLID) is now well recognised. ScienceDaily. Nicola P, Blackburn PR, Rasmussen KJ, Bertsch NL, Klee EW, Hasadsri L, Pichurin PN, Rankin J, Raymond FL; DDD Study, Clayton-Smith J. In summary, HUWE1 missense variants may cause syndromic ID in both males and females. Deciphering … The study represents important progress in understanding the molecular underpinnings of intellectual disability. In this study, high-throughput sequencing of the coding regions of the X-chromosome led to the identification of a missense variant in the HUWE1 gene. Missense mutations in HUWE1 occur in multiple families with intellectual disability, including families with Juberg-Marsidi-Brooks syndrome. Cell Rep Med. In affected individuals from 3 unrelated families with Turner-type X-linked syndromic mental retardation (MRXST; 309590), Froyen et al. E3 ubiquitin-protein ligase HUWE1 is an enzyme that in humans is encoded by the HUWE1 gene. 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. Biochem Soc Trans. HUWE1- related XLID affects both males and females. Essential E3 ubiquitin ligase HUWE1 (HECT, UBA, and WWE domain containing 1) regulates key factors, such as p53. Do People Aged 105 and Over Live Longer Because They Have More Efficient DNA Repair? In genetic (hereditary) causes, the exact identification of the defect is crucial for the medical supervision of the patient or to estimate the risk when having children. Bethesda, MD 20894, Copyright HUWE1 regulates essential processes such as genome integrity maintenance. Cerebellum: Key Role in Evolution of Human Brain, Sharks Use Earth's Magnetic Fields to Guide Them, Bats Know Speed of Sound from Birth: Study, Early Humans Changing Ecosystems With Fire. ScienceDaily. VIB researchers at KU Leuven show that increased production of the HUWE1 protein is the cause in some patients. Xp11.22 microduplications have been reported in different patients with X-linked intellectual disability. Through additional research, including the DNA of 6 additional families from Europe, Australia and South Africa, we now know that HUWE1 is the crucial factor, and that a concentration increase of HUWE1 leads to intellectual disability. 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? Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. It is not intended to provide medical or other professional advice. *Females with schizophrenia as indication for WES with de novo. In this review, we discuss how Huwe1 contributes to nervous system development, function and disease. In this work, we identify p53 signaling as the central process altered in … HUWE1. FOIA ScienceDaily, 31 August 2012. Please enable it to take advantage of the complete set of features! Two to three percent of children are born with an intellectual disability. Epub 2019 Feb 7. . Aprigliano R, Aksu ME, Bradamante S, Mihaljevic B, Wang W, Rian K, Montaldo NP, Grooms KM, Fordyce Martin SL, Bordin DL, Bosshard M, Peng Y, Alexov E, Skinner C, Liabakk NB, Sullivan GJ, Bjørås M, Schwartz CE, van Loon B. Moortgat S, Lederer D, Deprez M, Buzatu M, Clapuyt P, Boulanger S, Benoit V, Mary S, Guichet A, Ziegler A, Colin E, Bonneau D, Maystadt I. Eur J Med Genet. In 12 families with mild to moderate non-syndromic XLID, Froyen et al. De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability. Only rare non-synonymous and splice site variants are presented. It performs the third step (ligation) in binding ubiquitin to proteins in a process called ubiquitination which tags the proteins for disposal. (Refseq: NM_031407.6, NCBI Protein Reference…, X inactivation patterns in female patients in varying tissues and associated RNA expression…, Facial and limb features of individuals with HUWE1 variants, frontal and lateral views.…, National Library of Medicine This allows for tests to be designed with which the duplication of and errors in HUWE1 are searched. Here you will find a list of rare diseases related to the HUWE1. The advent of next-generation sequencing has proven to be a key force in the identification of new genes associated with intellectual disability. Increased gene dosage has been observed in males with non-syndromic mild to moderate ID with speech delay. This is called X-linked 'intellectual disability' (XLID). (Refseq: NM_031407.6, NCBI Protein Reference Sequence: NP_113584.3). Epub 2015 Nov 20. Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Guy Froyen: "We knew then that these two proteins could play an important role in the (development of) the memory center in the brains, but we did not yet know which gene was the cause for the increased dose of XLID. VIB. Views expressed here do not necessarily reflect those of ScienceDaily, its staff, its contributors, or its partners. , function and disease diagnosis based on your current symptoms variants may cause syndromic ID in obligate carrier females stature., and Distinct Facial features:51-6. doi: 10.1055/s-0035-1566233, Pisani F, Garavelli L, Pisani F Piccolo... 105 and Over Live Longer Because they have more Efficient DNA Repair latest science news with ScienceDaily 's email... 2019 Apr ; 179 ( 4 ):570-578. doi: 10.1002/ajmg.a.61061 ; 130 ( 12:6301-6316.... Syndromic ID in males appear viable and contribute to syndromic intellectual disability ''. Associated with the onset of neurodevelopmental disorders to intervene in these different proteins G, Pezzella M, F! 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