Recurrent tandem duplication of UNC13D in familial hemophagocytic lymphohistiocytosis type 3
Recurrent tandem duplication of UNC13D in familial hemophagocytic lymphohistiocytosis type 3
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DOI：
10.1016/j.clim.2022.109104
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发表时间：
2022-08-29
影响因子：
8.6
通讯作者：
Kanegane, Hirokazu
中科院分区：
文献类型：
--
作者：
Tomomasa, Dan;Hiejima, Eitaro;Kanegane, Hirokazu
家族性噬血细胞性淋巴组织细胞增生症3型是一种致命的先天性免疫缺陷，由于T和NK细胞的异常细胞毒性活性，并引起的UNC 13 D，编码Munc 13 -4的变体。一个已发表的情况下，进行串联重复UNC 13 D外显子7-12，我们在这里提出了另一个案件完全相同的重复断点。该患者携带来自母亲来源的串联重复，以及父亲等位基因上的c.2346_2349变体。对UNC 13 D的单核苷酸多态性分析显示，该串联重复等位基因最有可能是创始者等位基因。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。多序列比对显示，含有截短点的Alu元件高度同源。序列同源性被认为是诱发串联重复变体的因素。
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.