Loss‐of‐function CHD2 (chromodomain helicase DNA‐binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early‐onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families. We detect the first case of parental gonosomal CHD2 mosaicism disclosed by two brothers showing mild ID, born to healthy parents. The eldest brother has a history of drug‐controlled generalized tonic–clonic seizures and displays sleep disorder and aggressive behavior suggestive of Smith–Magenis syndrome (SMS). Analysis of brothers’ DNAs by next‐generation sequencing (NGS) custom gene panel for pediatric epilepsy and/or ID disclosed in both the same pathogenic CHD2 variant. Additional NGS experiment on genomic DNA from parents’ peripheral blood and from buccal swab raised the suspicion of low‐grade gonosomal mosaicism in the unaffected mother subsequently confirmed by digital polymerase chain reaction (dPCR). This report underlines as worthwhile CHD2 screening in individuals presenting ID/developmental delay, with/without epilepsy, and behavior and sleep disorders suggestive of SMS. Detecting a CHD2 variant should prime testing probands' parents by NGS coupled to dPCR on different tissues to exclude/confirm gonosomal mosaicism and define the recurrence risk.

中文翻译：

---

患有史密斯-马吉尼斯样综合征的 CHD2 兄弟姐妹中的低度父母性染色体嵌合

功能丧失冠心病2（染色质结构域解旋酶 DNA 结合蛋白 2）突变与一系列神经发育障碍相关，通常包括早发性全身性癫痫发作、光敏性和癫痫性脑病。患者表现出精神运动迟缓/智力障碍（ID）、自闭症特征和行为障碍，例如攻击性和冲动。大多数报告的病例都是散发的，仅在两个家庭中描述了种系嵌合。我们检测到第一例亲代性染色体冠心病2两兄弟披露了嵌合现象，他们表现出轻度智力障碍，他们的父母都是健康的。大哥有药物控制性全身强直阵挛性癫痫病史，并表现出睡眠障碍和攻击行为，提示患有史密斯-马吉尼斯综合征 (SMS)。通过下一代测序 (NGS) 定制基因组对兄弟 DNA 进行分析，用于治疗相同致病性中公开的儿童癫痫和/或 ID冠心病2变体。对父母外周血和口腔拭子的基因组 DNA 进行的额外 NGS 实验提出了未受影响母亲体内存在低级性染色体嵌合的怀疑，随后通过数字聚合酶链反应 (dPCR) 予以证实。这份报告强调了值得冠心病2对表现出智力障碍/发育迟缓、患有/不患有癫痫以及提示 SMS 的行为和睡眠障碍的个体进行筛查。检测到冠心病2变体应通过 NGS 结合不同组织的 dPCR 来初步检测先证者的父母，以排除/确认染色体嵌合并确定复发风险。