Bloemendaal Mirjam, Vlaming Priscilla, de Boer Anneke, Vermeulen-Kalk Karlijn, Bouman Arianne, Kleefstra Tjitske, Arias Vasquez Alejandro
Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2023 Oct-Dec;192(7-8):124-138. doi: 10.1002/ajmg.b.32926. Epub 2023 Jan 11.
Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. The clinical features of KS include intellectual disability, autistic behavior and gastrointestinal problems. The gut microbiota, an important modifier of the gut-brain-axis, may constitute an unexplored mechanism underlying clinical KS variation. We investigated the gut microbiota composition of 23 individuals with KS (patients) and 40 of their family members, to test whether (1) variation in the gut microbiota associates with KS diagnosis and (2) variation within the gut microbiota relates with KS syndrome symptoms. Both alpha and beta diversity of patients were different from their family members. Genus Coprococcus 3 was lower in abundance in patients compared to family members. Moreover, abundance of genus Merdibacter was lower in patients versus family members, but only in participants reporting intestinal complaints. Within the patient group, behavioral problems explained 7% of beta diversity variance. Also, within this group, we detected higher levels of Atopobiaceae - uncultured and Ruminococcaceae Subdoligranulum associated with higher symptom severity. These significant signatures in the gut microbiota composition in patients with KS suggest that microbiota differences are part of the KS phenotype.
克莱夫斯特拉综合征（KS）是一种罕见的单基因综合征，由常染色质组蛋白甲基转移酶1（EHMT1）基因的单倍剂量不足引起，该基因是神经发育的重要调节因子。KS的临床特征包括智力残疾、自闭症行为和胃肠道问题。肠道微生物群是肠-脑轴的重要调节因子，可能构成KS临床变异的一种未被探索的机制。我们调查了23名KS患者及其40名家庭成员的肠道微生物群组成，以测试（1）肠道微生物群的变异是否与KS诊断相关，以及（2）肠道微生物群内的变异是否与KS综合征症状相关。患者的α多样性和β多样性均与家庭成员不同。与家庭成员相比，患者体内的粪球菌属3丰度较低。此外，与家庭成员相比，患者体内的默迪氏菌属丰度较低，但仅在报告有肠道不适的参与者中如此。在患者组中，行为问题解释了7%的β多样性变异。此外，在该组中，我们检测到与较高症状严重程度相关的未培养阿托波氏菌科和瘤胃球菌科Subdoligranulum水平较高。KS患者肠道微生物群组成中的这些显著特征表明，微生物群差异是KS表型的一部分。
