The Jumonji domain containing 1C (JMJD1C) gene encodes the Jumonji domain-containing protein 1C (JMJD1C) and is a member of the jmJC domain-containing protein family involved in histone demethylation that is expressed in the brain. We report seven, unrelated patients with developmental delays or intellectual disability and heterozygous, de novo sequence variants in JMJD1C. All patients had developmental delays, but there were no consistent additional findings. Two patients were reported to have seizures for which there was no other identified cause. De novo, deleterious sequence variants in JMJD1C have previously been reported in patients with autism spectrum disorder and a phenotype resembling classical Rett syndrome, but only one JMJD1C variant has undergone functional evaluation. In all of the seven patients in this report, there was a plausible, alternative explanation for the neurocognitive phenotype or a modifying factor, such as an additional potentially pathogenic variant, presence of the variant in a population database, heteroplasmy for a mitochondrial variant or mosaicism for the JMJD1C variant. Although the de novo variants in JMJD1C are likely to be relevant to the developmental phenotypes observed in these patients, we conclude that further data supporting the association of JMJD1C variants with intellectual disability is still needed.

包含Jumonji域的1C（JMJD1C）基因编码包含Jumonji域的蛋白质1C（JMJD1C），并且是包含jmJC域的蛋白质家族的成员，参与了在大脑中表达的组蛋白去甲基化。我们报告了JMJD1C中有发育迟缓或智力残疾和杂合性，从头序列变异的7名无关患者。所有患者都有发育迟缓，但没有一致的其他发现。据报告有两名患者患有癫痫，没有其他原因可查。从头开始，JMJD1C中有害的序列变体先前已经报道了自闭症谱系障碍和类似经典雷特综合征的表型的患者，但是只有一种JMJD1C变体已经过功能评估。在本报告的所有7位患者中，对于神经认知表型或修饰因子（如其他潜在的致病变异体，变异体在人群数据库中的存在，线粒体变异体的异质性或镶嵌性）有一个合理的替代解释。用于JMJD1C变体。尽管JMJD1C中的从头变异可能与这些患者中观察到的发育表型有关，但我们得出结论，进一步的数据支持JMJD1C的关联 仍需要具有智力障碍的变体。