Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Genet Med. 2019 Jun;21(6):1295-1307. doi: 10.1038/s41436-018-0330-z. Epub 2018 Nov 8.
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.
Clinicians entered clinical data in an extensive web-based survey.
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.
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.
通过大规模外显子组测序研究发现，ARID1B 中的致病变异是智力障碍（ID）的最常见原因之一。迄今为止，大多数已发表的研究都描述了经临床诊断的 Coffin-Siris 患者（ARID1B-CSS），尚不清楚这些数据是否代表通过对无偏 ID 队列进行测序而确定的患者（ARID1B-ID）。因此，我们试图确定 ARID1B-ID 和 ARID1B-CSS 之间的基因型和表型差异。同时，我们研究了不同表型报告方法的效果。
临床医生在一个广泛的基于网络的调查中输入了临床数据。
纳入了 79 名 ARID1B-CSS 和 64 名 ARID1B-ID 患者。CSS 相关的畸形特征，如浓眉、长睫毛、鼻翼宽厚、长而/或宽的人中、小指甲和小或无第五远节指骨和多毛症，在 ARID1B-CSS 患者中观察到的频率明显更高（p<0.001）。未发现其他显著差异。
ARID1B-ID 和 ARID1B-CSS 患者之间仅有细微差异。ARID1B 相关疾病似乎存在一个谱，患者应类似地进行管理。我们证明，没有明确报告特征缺失选项的数据收集方法（例如大多数基于人类表型本体的方法）往往会低估与基因相关的特征。
