Early infantile ‐onset epileptic encephalopathy 28 due to a homozygous microdeletion involving the WWOX gene in a region of uniparental disomy

This report describes a rare autosomal recessive disorder with multiple genetic etiologies, one that involves uniparental disomy. A 6 ‐year‐old girl was admitted to the NIH Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, facial dysmorphisms, and skeletal abnormalities. Chromosome 16q22.1–16q24.3 uniparental disomy, included a maternally inherited homozygous microdeletion coveri ng exon 6 ofWWOX (NM_016373.3), which could cause the seizures and intellectual disability. Additional pathogenic compound heterozygous variants inHSPG2 are likely responsible for the patient's skeletal abnormalities. AbstractThe genetic etiologies of many rare disorders, including early infantile epileptic encephalopathies, are largely undiagnosed. A 6 ‐year‐old girl was admitted to the National Institutes of Health Undiagnosed Diseases Program with profound intellectual disability, infantile‐onset seizures, chronic respiratory failure, facial dysmorphisms, skeletal abnormalities, and atrial septum defect. A large region of homozygosity was discovered on chromosome 16, spanning 16q22.1–16q24.3' caused by uniparental disomy (UPD) that included a maternally inherited homozygous microdeletion covering exon 6 ofWWOX (NM_016373.3). mRNA expression analysis revealed that the deletion led to nonsense ‐mediated decay of the NM_016373.3 transcript; the exon 6 of an alternative transcript (NM_130791.3), lacking the short‐chain dehydrogena...
Source: Human Mutation - Category: Genetics & Stem Cells Authors: Tags: BRIEF REPORT Source Type: research

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In this study, we performed an extensive assessment of the value of CMA for the diagnosis of children with ID/DD in China. Methods: A total of 633 patients diagnosed with DD/ID in West China Second University Hospital, Sichuan University, were recruited from January 2014 to March 2019. The patients were classified into 4 subgroups: isolated DD/ID, DD/ID with multiple congenital anomalies (MCA), isolated autism spectrum disorders (ASDs), and DD/ID with epilepsy. CMA was performed on Affymetrix 750K platform. Results: Among the 633 patients, 127 cases were identified as having pathogenic copy number variations (pCN...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
We present a patient with 17q12 deletion syndrome with significant atopy.
Source: Annals of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Source Type: research
Publication date: Available online 5 August 2019Source: The Lancet PsychiatryAuthor(s): Janneke R Zinkstok, Erik Boot, Anne S Bassett, Noboru Hiroi, Nancy J Butcher, Claudia Vingerhoets, Jacob A S Vorstman, Therese A M J van AmelsvoortSummary22q11.2 deletion syndrome is characterised by a well defined microdeletion that is associated with a high risk of neuropsychiatric disorders, including intellectual disability, schizophrenia, attention-deficit hyperactivity disorder, autism spectrum disorder, anxiety disorders, seizures and epilepsy, and early-onset Parkinson's disease. Preclinical and clinical data reveal substantial ...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
ConclusionThe presented patient is the second with a pathogenicMBD5 mutation in whom the course of disease is suggestive of early onset dementia starting in her fifth decade. These findings stress the importance of exome sequencing, also in elderly intellectually disabled patients, particularly in those with autism.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
In conclusion, the 6q27 microdeletion is a complex syndrome with variable expressivity of brain malformations and intellectual disability phenotypes which are possibly triggered by the 4 genes described and adjacent genes susceptible to gene regulation changes.Mol Syndromol
Source: Molecular Syndromology - Category: Molecular Biology Source Type: research
ConclusionThis report highlights the potential of aCGH as a practical and powerful tool with which to detect submicroscopic chromosomal abnormalities in individuals presenting with a wide spectrum of phenotypes, ranging from facial dysmorphism to failure to thrive. Additionally, the literature review casts new light on the clinical features of 20p13 microdeletion.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
Conclusions: Almost one-third of ASD patients in our sample had at least one fGID. The presence of fGID was associated with ID, sleep problems and with behavioral problems (as measured by the prescription of psychotropic drugs). This subsample of ASD patients with fGID deserves particular attention in future research projects, focusing on specific phenotypic characteristics and overlapping biological markers that may underlie both pathologies. Introduction Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impairments in social communication and restricted, repetitive patterns ...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
We report on 2 brothers, aged 7.6 and 20 years, presenting with cognitive impairment, epilepsy, autistic features, hearing loss, and obesity. Array-CGH analysis demonstrated 2 rare CNVs in both siblings: a paternally inherited microdeletion of ∼145 kb at 3p22.1, disrupting theULK4 gene, and a maternally inherited microduplication of ∼117 kb at Xq21.1 including only theBRWD3 gene. As already described for other recurrent syndromes with variable phenotype, these findings are challenging in genetic counseling because of an evident variable penetrance. We discuss the possible correlations between the clinical phenotype...
Source: Cytogenetic and Genome Research - Category: Genetics & Stem Cells Source Type: research
We report on 2 brothers, aged 7.6 and 20 years, presenting with cognitive impairment, epilepsy, autistic features, hearing loss, and obesity. Array-CGH analysis demonstrated 2 rare CNVs in both siblings: a paternally inherited microdeletion of ∼145 kb at 3p22.1, disrupting theULK4 gene, and a maternally inherited microduplication of ∼117 kb at Xq21.1 including only theBRWD3 gene. As already described for other recurrent syndromes with variable phenotype, these findings are challenging in genetic counseling because of an evident variable penetrance. We discuss the possible correlations between the clinical phenotype...
Source: Cytogenetic and Genome Research - Category: Genetics & Stem Cells Source Type: research
Publication date: July 2018Source: The Lancet Psychiatry, Volume 5, Issue 7Author(s): Line Olsen, Thomas Sparsø, Shantel M Weinsheimer, Marcelo Bertalan Quintanilha Dos Santos, Wiktor Mazin, Anders Rosengren, Xabier Calle Sanchez, Louise K Hoeffding, Henriette Schmock, Marie Baekvad-Hansen, Jonas Bybjerg-Grauholm, Mark J Daly, Benjamin M Neale, Marianne G Pedersen, Esben Agerbo, Ole Mors, Anders Børglum, Merete Nordentoft, David M Hougaard, Preben Bo MortensenSummaryBackgroundAlthough the pathogenic nature of copy number variants (CNVs) on chromosome 22q11.2 has been recognised for decades, unbiased estimates...
Source: The Lancet Psychiatry - Category: Psychiatry Source Type: research
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