Title |
Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability
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Published in |
Journal of Medical Genetics, September 2017
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DOI | 10.1136/jmedgenet-2017-104759 |
Pubmed ID | |
Authors |
Genay O Pilarowski, Hilary J Vernon, Carolyn D Applegate, Leandros Boukas, Megan T Cho, Christina A Gurnett, Paul J Benke, Erin Beaver, Jennifer M Heeley, Livija Medne, Ian D Krantz, Meron Azage, Dmitriy Niyazov, Lindsay B Henderson, Ingrid M Wentzensen, Berivan Baskin, Maria J Guillen Sacoto, Gregory D Bowman, Hans T Bjornsson |
Abstract |
The list of Mendelian disorders of the epigenetic machinery has expanded rapidly during the last 5 years. A few missense variants in the chromatin remodeler CHD1 have been found in several large-scale sequencing efforts focused on uncovering the genetic aetiology of autism. To explore whether variants in CHD1 are associated with a human phenotype. We used GeneMatcher to identify other physicians caring for patients with variants in CHD1. We also explored the epigenetic consequences of one of these variants in cultured fibroblasts. Here we describe six CHD1 heterozygous missense variants in a cohort of patients with autism, speech apraxia, developmental delay and facial dysmorphic features. Importantly, three of these variants occurred de novo. We also report on a subject with a de novo deletion covering a large fraction of the CHD1 gene without any obvious neurological phenotype. Finally, we demonstrate increased levels of the closed chromatin modification H3K27me3 in fibroblasts from a subject carrying a de novo variant in CHD1. Our results suggest that variants in CHD1 can lead to diverse phenotypic outcomes; however, the neurodevelopmental phenotype appears to be limited to patients with missense variants, which is compatible with a dominant negative mechanism of disease. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 77 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 16% |
Student > Ph. D. Student | 8 | 10% |
Student > Doctoral Student | 7 | 9% |
Student > Bachelor | 7 | 9% |
Student > Master | 5 | 6% |
Other | 11 | 14% |
Unknown | 27 | 35% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 20 | 26% |
Neuroscience | 8 | 10% |
Agricultural and Biological Sciences | 6 | 8% |
Medicine and Dentistry | 6 | 8% |
Psychology | 4 | 5% |
Other | 5 | 6% |
Unknown | 28 | 36% |