Objective: 

Causative variants in SETD1B, encoding a lysine-specific methyltransferase, have recently been associated with a neurodevelopmental phenotype encompassing intellectual disability, autistic features, pronounced language delay, and epilepsy. It has been noted that long-term and deep phenotype data are needed to further delineate this rare condition.

Methods: 

In this study, we provide an in-depth clinical characterization with long-term follow-up and trio exome sequencing findings to describe one additional individual affected by SETD1B-related disorder. The diagnostic workup was complemented by a functional magnetic resonance imaging (fMRI) study.

Results: 

We report a 24-year-old male individual with an early-onset neurodevelopmental disorder with epilepsy due to the de novo missense variant c.5699A>G, p.(Tyr1900Cys) in SETD1B (NM_015048.1). He exhibited delayed speech development, autism spectrum disorder, and early-onset epilepsy with absence and generalized tonic-clonic seizures. Despite profoundly impaired communication skills, ongoing improvements regarding language production have been noted in adulthood. fMRI findings demonstrate abnormal language activation and resting-state connectivity structure.

Conclusion: 

Our report expands the previously delineated phenotype of SETD1B-related disorder and provides novel insights into underlying disease mechanisms.

中文翻译：

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SETD1B 相关神经发育障碍和癫痫患者的连接组分析

客观的： 

SETD1B中的致病变异，编码赖氨酸特异性甲基转移酶，最近与神经发育表型相关，包括智力障碍、自闭症特征、明显的语言延迟和癫痫。已经注意到需要长期和深入的表型数据来进一步描述这种罕见的情况。

方法： 

在这项研究中，我们通过长期随访和三外显子组测序结果提供了深入的临床特征，以描述另一个受SETD1B相关疾病影响的个体。功能性磁共振成像 (fMRI) 研究补充了诊断检查。

结果： 

我们报告了一名 24 岁男性个体，患有早发性神经发育障碍伴癫痫，原因是 SETD1B (NM_015048.1) 中的从头错义变异 c.5699A>G, p.( Tyr1900Cys )。他表现出语言发育迟缓、自闭症谱系障碍和早发性癫痫伴失神和全身强直-阵挛发作。尽管沟通技巧严重受损，但在成年期已经注意到语言生产方面的持续改善。fMRI 发现显示异常的语言激活和静息状态连接结构。

结论： 

我们的报告扩展了先前描述的SETD1B相关疾病的表型，并为潜在的疾病机制提供了新的见解。