Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Clin Immunol. 2022 Sep;242:109104. doi: 10.1016/j.clim.2022.109104. Epub 2022 Aug 27.
Familial hemophagocytic lymphohistiocytosis type 3 is a fatal inborn error of immunity due to abnormal cytotoxic activity of T and NK cells and is caused by variants in UNC13D, which encodes Munc13-4. One published case was reported to carry a tandem duplication of UNC13D exons 7-12, and we here present another case with the exact same duplication breakpoints. The patient carried the tandem duplication from maternal origin, and a c.2346_2349 variant on the paternal allele. Single nucleotide polymorphism analysis around UNC13D revealed that the allele with tandem duplication was most likely a founder allele. Transposable element analysis showed that the breakpoints occurred within Alu elements in introns 12 and 6. Multiple sequence alignment revealed that Alu elements containing the truncated points are highly homologous. Sequence homology was thought to be a factor predisposing to the tandem duplication variant.
家族性噬血细胞性淋巴组织细胞增生症 3 型是一种致命的遗传性免疫缺陷病，由于 T 细胞和 NK 细胞的细胞毒性活性异常，由 UNC13D 变异引起，该基因编码 Munc13-4。曾有报道称一例患者携带 UNC13D 外显子 7-12 的串联重复，我们在此报告另一例具有相同重复断裂点的病例。患者从母源携带串联重复，从父源携带 c.2346_2349 变异。UNC13D 周围的单核苷酸多态性分析显示，串联重复的等位基因很可能是一个起始等位基因。转座元件分析表明，断裂点发生在内含子 12 和 6 的 Alu 元件内。多重序列比对显示，含有截断点的 Alu 元件具有高度同源性。序列同源性被认为是串联重复变异的一个易感因素。
