Alvarez-Mora Maria Isabel, Calvo Escalona Rosa, Puig Navarro Olga, Madrigal Irene, Quintela Ines, Amigo Jorge, Martinez-Elurbe Dei, Linder-Lucht Michaela, Aznar Lain Gemma, Carracedo Angel, Mila Montserrat, Rodriguez-Revenga Laia
Biochemistry and Molecular Genetics Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain; CIBER of Rare Diseases (CIBERER), Villarroel 170, 08036 Barcelona, Spain; IDIBAPS, Rosselló 149, 08036 Barcelona, Spain.
Child and Adolescent Psychiatry Department, Hospital Clinic, SGR-1119, CIBERSAM, Villarroel 170, 08036 Barcelona, Spain.
Mutat Res. 2016 Feb-Mar;784-785:46-52. doi: 10.1016/j.mrfmmm.2015.12.006. Epub 2016 Jan 6.
Autism spectrum disorders (ASD) include a range of complex neurodevelopmental disorders with extreme genetic heterogeneity. Exome and target sequencing studies have shown to be an effective tool for the discovery of new ASD genes. The aim of this study was to design an ASD candidate gene panel that covers 44 of the top ASD candidate genes. As a pilot study we performed comprehensive molecular diagnostic testing, including the study of the FMR1 and FMR2 repeat regions, copy number variant analysis in a collection of 50 Spanish ASD cases and mutation screening using targeted next generation sequencing-based techniques in 44 out of the total cohort. We evaluated and clinically selected our cohort, with most of the cases having high functioning ASD without facial dysmorphic features. The results of the present study allowed the detection of copy number and single nucleotide variants not yet identified. In addition, our results underscore the difficulty of the molecular diagnosis of ASD and confirm its genetic heterogeneity. The information gained from this and other genetic screenings is necessary to unravel the clinical interpretation of novel variants.
自闭症谱系障碍（ASD）包括一系列具有极端遗传异质性的复杂神经发育障碍。外显子组测序和靶向测序研究已被证明是发现新的ASD基因的有效工具。本研究的目的是设计一个涵盖44个顶级ASD候选基因的ASD候选基因面板。作为一项试点研究，我们进行了全面的分子诊断测试，包括对FMR1和FMR2重复区域的研究、对50例西班牙ASD病例进行拷贝数变异分析，以及在整个队列中的44例中使用基于靶向新一代测序的技术进行突变筛查。我们对队列进行了评估并进行临床选择，大多数病例为高功能ASD且无面部畸形特征。本研究结果使得能够检测到尚未识别的拷贝数和单核苷酸变异。此外，我们的结果强调了ASD分子诊断的困难，并证实了其遗传异质性。从本次及其他基因筛查中获得的信息对于阐明新变异的临床解释是必要的。
