PurposePathogenic 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.MethodsClinicians entered clinical data in an extensive web-based survey.Results79 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.ConclusionThere 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.

The usefulness of peak expiratory flow monitoring is disputed because of the unreliability of written peak flow diaries. The aim of the present study was to examine the relationship of peak flow and forced expiratory volume in one second (FEV1) variation to other estimates of asthma severity in children, using an electronic home spirometer with automatic data storage.Over a 3-month period, 36 children with mild-to-moderate persistent asthma recorded peak flow and FEV1 electronically twice daily and noted an asthma severity score in a written diary. Bronchial responsiveness was assessed at the beginning and bronchodilator response and asthma-specific quality of life at the end of the study.Variations in peak flow correlated significantly but weakly to bronchial responsiveness and bronchodilator response, but not to the asthma severity score or quality-of-life scores. Withinindividual correlations between asthma severity scores and home spirometry indices and between peak flow and FEV1 were highly variable.In conclusion, variations in peak flow and forced expiratory volume in one second, obtained by home spirometry, show poor concordance with other indices of disease activity and with each other. This limits the usefulness of home spirometry in childhood asthma.

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