McDermott J H, Study D D D, Clayton-Smith J, Briggs T A
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals, NHS Foundation Trust Manchester Academic Health Sciences Centre, United Kingdom; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
Wellcome Trust Sanger Institute, Cambridgeshire, United Kingdom.
Eur J Med Genet. 2018 May;61(5):253-256. doi: 10.1016/j.ejmg.2017.12.009. Epub 2017 Dec 27.
A diverse range of genetic aberrations can lead to Autistic Spectrum Disorder (ASD) and many of these have been identified via Next Generation Sequencing (NGS) as part of large scale consortium studies. ASD is a phenotypically variable disorder and detailed clinical descriptions are essential to appreciate genotype-phenotype relationships. In this report, we provide a comprehensive clinical description of a child with ASD in whom a TBR1 variant was identified. We review this case in the context of the current TBR1 literature and highlight the variable spectrum of disease associated with this gene. The phenotypic information outlined within the literature is incomplete, exemplifying the limitations of massively-parallel sequencing studies with regards to clinical annotation. We suggest that future reporting of ASD variants should include standardised phenotypic descriptions. This would develop a more thorough understanding of genotype-phenotype relationship, so allowing us to better counsel and support our patients.
多种基因畸变可导致自闭症谱系障碍（ASD），其中许多已通过下一代测序（NGS）作为大规模联合研究的一部分被鉴定出来。ASD是一种表型多样的疾病，详细的临床描述对于理解基因型-表型关系至关重要。在本报告中，我们提供了一名患有ASD且鉴定出TBR1变异的儿童的全面临床描述。我们在当前TBR1文献的背景下回顾此病例，并强调与该基因相关的疾病谱的变异性。文献中概述的表型信息不完整，体现了大规模平行测序研究在临床注释方面的局限性。我们建议，未来关于ASD变异的报告应包括标准化的表型描述。这将有助于更全面地理解基因型-表型关系，从而使我们能够更好地为患者提供咨询和支持。
