A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia
A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia
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DOI：
10.1159/000518227
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发表时间：
2021-09
影响因子：
2.4
通讯作者：
S. Tamura;H. Kosako;Yoshiaki Furuya;Yusuke Yamashita;Toshiki Mushino;H. Mishima;A. Kinoshita;A. Nishikawa;K. Yoshiura;T. Sonoki
中科院分区：
文献类型：
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作者：
S. Tamura;H. Kosako;Yoshiaki Furuya;Yusuke Yamashita;Toshiki Mushino;H. Mishima;A. Kinoshita;A. Nishikawa;K. Yoshiura;T. Sonoki
歌舞伎综合征(KS)是一种罕见的先天性疾病，常合并体液免疫缺陷。KS患者存在组蛋白赖氨酸N甲基转移酶2D(KMT2D)基因突变。尽管在淋巴瘤和白血病中经常发现各种KMT2D突变，但在再生障碍性贫血(AA)中遇到的突变是有限的。在此，我们报告一位45岁的日本男子，他出现严重的全血细胞减少症和低丙种球蛋白血症。他没有表现出任何明显的畸形、智力残疾或可检测到的自身抗体水平。然而，B细胞的发育受到了损害。因此，诊断为非常严重的再生障碍性贫血是由于骨髓发育不良，对粒细胞集落刺激因子无效。患者接受了脐带血移植，但在中性粒细胞植入前死于假单胞菌感染。三个全外显子测序发现KMT2D基因第50外显子存在一个新的错义杂合突变c.15959G>；A(p.R5320H)。此外，外周血和骨髓单个核细胞的Sanger测序以及从该患者获得的皮肤活检标本证实了该杂合突变，表明与KS相关的从头突变发生在早期胚胎发育中。我们的病例显示KS突变与成人起病再生障碍性贫血之间存在新的关联。
Kabuki syndrome (KS) is a rare congenital disorder commonly complicated by humoral immunodeficiency. Patients with KS present with mutation in the histone-lysine N-methyltransferase 2D (KMT2D) gene. Although various KMT2D mutations are often identified in lymphoma and leukemia, those encountered in aplastic anemia (AA) are limited. Herein, we present the case of a 45-year-old Japanese man who developed severe pancytopenia and hypogammaglobulinemia. He did not present with any evident malformations, intellectual disability, or detectable levels of autoantibodies. However, B-cell development was impaired. Therefore, a diagnosis of very severe AA due to a hypoplastic marrow, which did not respond to granulocyte colony-stimulating factor, was made. The patient received umbilical cord blood transplantation but died from a Pseudomonas infection before neutrophil engraftment. Trio whole-exome sequencing revealed a novel missense heterozygous mutation c.15959G >A (p.R5320H) in exon 50 of the KMT2D gene. Moreover, Sanger sequencing of peripheral blood and bone marrow mononuclear cells and a skin biopsy specimen obtained from this patient identified this heterozygous mutation, suggesting that de novo mutation associated with KS occurred in the early embryonic development. Our case showed a novel association between KS mutation and adult-onset AA.