KDM3B is located on chromosome 5q31 and encodes KDM3B, which is involved in histone demethylation and epigenetic regulation. Pathogenic KDM3B variants cause a dominantly inherited disorder presenting with intellectual disability (ID), short stature, and facial dysmorphism, named Diets–Jongmans syndrome. We describe two patients with KDM3B variants presenting with Diets–Jongmans syndrome. Genetic testing was performed because of the clinical data and a lack of a clear diagnosis in both patients. Candidate variants were verified by Sanger sequencing. After KDM3B variants were detected, in silico tools were used to predict the pathogenicity of the missense variants. A minigene assay was performed to evaluate the splicing effects of the c.5070 + 1G > A variant on KDM3B. Patient 1 mainly presented with repetitive upper respiratory tract infection and patient 2 presented with palpitation, shortness of breath, and pitting edema; both had ID. Whole exome sequencing identified variants of KDM3B. Patient 1 had the de novo KDM3B c.5070 + 1G > A variant, whereas patient 2 had the c.2828G > A (p.R943Q) variant. Transcriptional experiments of the splicing variant c.5070 + 1G > A revealed aberrant transcripts leading to truncated protein products. We found two pathogenic variants in KDM3B, one of which is novel. Both patients had additional clinical presentations, and patient 1 had transient neutropenia. KDM3B c.5070 + 1G > A is the first KDM3B splice-site variant and was identified as a germline variant. Neutropenia and cardiomyopathy are newly found presentations of Diets–Jongmans syndrome. Our report enriches our knowledge of the genotypic spectrum of the KDM3B variants and phenotypic diversity of Diets–Jongmans syndrome.

KDM3B位于染色体5q31，编码KDM3B，参与组蛋白去甲基化和表观遗传调控。致病性KDM3B变异导致显性遗传疾病，表现为智力障碍 (ID)、身材矮小和面部畸形，称为 Diets-Jongmans 综合征。我们描述了两名患有 Diets-Jongmans 综合征的KDM3B变异患者。由于两名患者的临床数据和缺乏明确诊断，因此进行了基因检测。候选变体通过 Sanger 测序验证。KDM3B之后检测到变异后，使用计算机工具预测错义变异的致病性。进行小基因测定以评估 c.5070 + 1G > A 变体对KDM3B的剪接效果。患者1主要表现为反复上呼吸道感染，患者2表现为心慌、气短、凹陷性水肿；都有身份证。全外显子组测序鉴定了KDM3B的变体。患者 1 具有从头KDM3B c.5070 + 1G > A 变体，而患者 2 具有 c.2828G > A (p.R943Q) 变体。剪接变体 c.5070 + 1G > A 的转录实验揭示了导致截短蛋白质产物的异常转录本。我们在KDM3B中发现了两个致病变异，其中一个是新颖的。两名患者都有其他临床表现，患者 1 有短暂性中性粒细胞减少症。KDM3B c.5070 + 1G > A 是第一个KDM3B剪接位点变体，被确定为种系变体。中性粒细胞减少症和心肌病是新发现的 Diets-Jongmans 综合征的表现。我们的报告丰富了我们对KDM3B变体的基因型谱和 Diets-Jongmans 综合征的表型多样性的了解。