Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while CHD5-related disorders are still unknown. Thanks to GeneMatcher and international collaborations, we assembled a cohort of 16 unrelated individuals harboring heterozygous CHD5 variants, all identified by exome sequencing. Twelve patients had de novo CHD5 variants, including ten missense and two splice site variants. Three familial cases had nonsense or missense variants segregating with speech delay, learning disabilities, and/or craniosynostosis. One patient carried a frameshift variant of unknown inheritance due to unavailability of the father. The most common clinical features included language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%). Epilepsy types were variable, with West syndrome observed in three patients, generalized tonic-clonic seizures in two, and other subtypes observed in one individual each. Our findings suggest that, in line with other CHD-related disorders, heterozygous CHD5 variants are associated with a variable neurodevelopmental syndrome that includes intellectual disability with speech delay, epilepsy, and behavioral problems as main features.
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http://dx.doi.org/10.1007/s00439-021-02283-2 | DOI Listing |
Trials
December 2024
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Background: Autistic people commonly have physical and mental health conditions. They also frequently experience barriers to accessing healthcare, contributing to problems identifying and treating health conditions. These factors may lead to increased and earlier morbidity and lower average life expectancy for autistic people.
View Article and Find Full Text PDFJ Med Genet
December 2024
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Background: Clinical trials for rare disorders have unique challenges due to low prevalence, patient phenotype variability and high expectations. These challenges are highlighted by our study on clonazepam in patients, a common cause of intellectual disability. Previous studies on Arid1b-haploinsufficient mice showed positive effects of clonazepam on various cognitive aspects.
View Article and Find Full Text PDFEur J Med Genet
December 2024
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark; Centre for Rare Diseases, Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
KAT6A syndrome or Arboleda-Tham Syndrome (ARTHS; OMIM #616268) is a syndromic neurodevelopmental disorder mainly presenting with variable degrees of intellectual disability (ID) and developmental delay (DD), especially speech delay, hypotonia and autism spectrum disorders/behavioral problems. Multiple organ-systems including eyes, heart, gastrointestinal and neurological system can be involved. Other phenotypic features with a suggested association to KAT6A include immune dysfunction and pituitary anomalies.
View Article and Find Full Text PDFInt J Qual Health Care
December 2024
Lisbon Institute of Global Mental Health, Comprehensive Health Research Centre/NOVA Medical School, National School of Public Health, NOVA University of Lisbon. Rua do Instituto Bacteriológico 5, Edifício Amarelo, 1150-190 Lisbon, Portugal.
Background: Lithuania ratified the UN Convention on the Rights of Persons with Disabilities (UNCRPD) in 2010 and started deinstitutionalisation in 2014. This reform covers segregated social care institutions where persons with mental health conditions, psychosocial and/or intellectual disabilities live. It aims to move away from institutional care and towards community-based services.
View Article and Find Full Text PDFJ Appl Genet
December 2024
Psychological Counselling for Rare Genetic Diseases, Institute of Psychology, Faculty of Social Science, University of Gdansk, Bażynskiego, 4, 80-309, Gdańsk, Poland.
This case study presents a comprehensive analysis of the neurocognitive, medical, and developmental functioning of a 9-year-old girl diagnosed with mucopolysaccharidosis type IIIC (MPS IIIC). Genetic testing revealed a homozygous pathogenic variant of the HGSNAT gene (c.1872C > A), typically associated with severe neurodegeneration.
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