Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7016, Cincinnati, OH, 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
BMC Pediatr. 2024 Jan 11;24(1):34. doi: 10.1186/s12887-023-04510-3.
Familial hemophagocytic lymphohistiocytosis (FHL) is an immunological disorder characterized by overactivation of macrophages and T lymphocytes. This autosomal recessive condition has been characterized into multiple types depending on the genetic etiology. FHL type 3 is associated with bi-allelic pathogenic variants in the UNC13D gene.
We present a 12-year diagnostic odyssey for a family with FHL that signifies the advances of FHL genetic testing in a clinical genetic diagnostic laboratory setting. We describe the first case of a large UNC13D gross deletion in trans to a nonsense variant in a family with FHL3, which may have been mediated by Alu elements within introns 12 and 25 of the UNC13D gene.
This case highlights the importance of re-evaluating past genetic testing for a patient and family as test technology evolves in order to end a diagnostic odyssey.
家族性噬血细胞性淋巴组织细胞增生症（FHL）是一种免疫失调性疾病，其特征为巨噬细胞和 T 淋巴细胞过度激活。根据遗传病因，这种常染色体隐性疾病已被分为多种类型。FHL 型 3 与 UNC13D 基因的双等位致病性变异有关。
我们介绍了一个有 FHL 家族长达 12 年的诊断探索历程，这标志着 FHL 遗传检测在临床遗传诊断实验室环境中的进展。我们描述了第一个 UNC13D 大片段缺失与 FHL3 中的无义变异呈反式共有的病例，这可能是 UNC13D 基因的内含子 12 和 25 内的 Alu 元件介导的。
本病例强调了随着检测技术的发展，为了结束诊断探索，重新评估患者和家族过去的基因检测的重要性。
