Abstract：
Objective: The clinical and genetic characteristics of a child with inherited bone marrow failure syndrome as prominent clinical manifestations and special facial features were analyzed, and the etiology and mechanism were explored in, combination with clinical practice. Methods: Blood samples and clinical information were collected separately from the proband and their biological parents. The pathogenic variant was verified using next-generation sequencing technology screening, and the candidate variable sites were confirmed by using Sanger sequencing among all members of the family. Results: A heterozygous nonsense mutation in exon 17 of KAT6A (NM_006766), c.4177G > T (p.E1393*) predicted to cause truncation within the acidic domain of the protein was identified. Pedigree analysis did not reveal any variation in this locus between the proband\'s father and mother. No report of this pathogenic variant was found in a literature search of domestic and foreign databases, indicating that it is a newly discovered mutation. According to the guidelines of the American College of Medical Genetics, the variation was preliminarily determined to be a pathogenic. The newly discovered heterozygous mutation in KAT6A may be the cause of the disease in this child. Additionally, inherited bone marrow failure syndrome is a prominent manifestation. Conclusion: This study not only provides us with an in-depth understanding of this rare syndrome but also deepens our understanding of the function of KAT6A.
摘要：
目的:分析1例遗传性骨髓衰竭综合征患儿的临床及遗传特点,并对病因和机制进行了探索，结合临床实践。方法：分别收集先证者及其亲生父母的血液样本和临床资料。致病性变异采用下一代测序技术筛选,通过使用Sanger测序在该家族的所有成员中确认候选可变位点。结果:KAT6A(NM_006766)第17外显子发生杂合无义突变,c.4177G>T（p。E1393*)预测在蛋白质的酸性结构域内引起截短。谱系分析未显示先证者父亲和母亲之间该基因座的任何差异。在国内外数据库的文献检索中没有发现这种致病变异的报道,表明这是一种新发现的突变。根据美国医学遗传学学院的指导方针，初步确定该变异是致病的。KAT6A中新发现的杂合突变可能是该儿童疾病的原因。此外,遗传性骨髓衰竭综合征是一个突出的表现。结论：本研究不仅为我们提供了对这种罕见综合征的深入了解，而且加深了我们对KAT6A功能的理解。
