Publication: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome
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van der Sluijs, Pleuntje J.
Jansen, Sandra
Vergano, Samantha A.
Adachi-Fukuda, Miho
Alanay, Yasemin
AlKindy, Adila
Baban, Anwar
Bayat, Allan
Beck-Woedl, Stefanie
Berry, Katherine
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English
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Abstract
Purpose: pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: there are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features.
Source:
Genetics in Medicine
Publisher:
Nature Publishing Group (NPG)
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Subject
Medicine, Genetics and heredity