Severe Combined Immunodeficiency (SCID) is a genetically heterogeneous group of disorders characterized by severe T cell lymphopenia and defective T and B cell function. Without prompt diagnosis and early intervention, patients with SCID typically die from infection within the first year of life. Advances in molecular genetics have led to rapid and efficient diagnosis of SCID cases, particularly when paired with newborn screening. However, some cases remain unsolved, and this is of particular relevance to families that plan to have more children. Here we report a patient who died from complications of SCID in whom whole exome sequencing failed to reveal a candidate variant. We describe how Sanger sequencing of parents was used to study the genomic regions that were poorly covered by WES, and how immune phenotyping results were used in the setting of genetic counseling.

严重的免疫缺陷综合症（SCID）是一组遗传异质性疾病，其特征是严重的T细胞淋巴细胞减少以及T细胞和B细胞功能缺陷。如果没有及时诊断和早期干预，SCID患者通常会在生命的第一年内死于感染。分子遗传学的发展已导致对SCID病例的快速有效诊断，尤其是与新生儿筛查配对时。但是，有些案件仍未解决，这与计划生育更多孩子的家庭特别相关。在这里，我们报告了一名因SCID并发症而死亡的患者，该患者的整个外显子组测序均未能揭示出候选变异。我们描述了如何使用Sanger父母双亲测序来研究WES覆盖较差的基因组区域，