Valentino Floriana, Bruno Lucia Pia, Doddato Gabriella, Giliberti Annarita, Tita Rossella, Resciniti Sara, Fallerini Chiara, Bruttini Mirella, Lo Rizzo Caterina, Mencarelli Maria Antonietta, Mari Francesca, Pinto Anna Maria, Fava Francesca, Baldassarri Margherita, Fabbiani Alessandra, Lamacchia Vittoria, Benetti Elisa, Zguro Kristina, Furini Simone, Renieri Alessandra, Ariani Francesca
Medical Genetics, University of Siena, 53100 Siena, Italy.
Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Brain Sci. 2021 Jul 16;11(7):936. doi: 10.3390/brainsci11070936.
Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: and . In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that "reverse phenotyping" is fundamental to enlarge the phenotypic spectra associated with specific genes.
智力残疾（ID）和自闭症谱系障碍（ASD）属于神经发育障碍，在一般人群中的发生率约为1%。由于疾病的异质性，确定ID和ASD的病因仍然具有挑战性。外显子组测序（ES）为快速识别与这两种常共存的疾病相关的变异提供了机会。在此，我们对200名患者进行了ES检测：84名孤立性ID患者和116名ID合并ASD患者。我们鉴定出41个致病变异，检出率为22%（43/200）：ID患者中为39%（33/84），ID/ASD患者中为9%（10/116）。大多数致病基因是与已明确的遗传综合征相关的基因，这些综合征此前未因非典型表型而被识别。有两个基因成为新的候选基因： 和 。总之，本研究强化了ES在ID/ASD诊断中的重要性，并强调“反向表型分析”对于扩大与特定基因相关的表型谱至关重要。
