The membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene codes for an enzyme involved in regulating arachidonic acid incorporation in lysophosphatidylinositol. Patients with homozygous nonsense mutations in MBOAT7 have intellectual disability (ID) accompanied with seizure and autism. Accumulating evidences obtained from human genetic studies have shown that MBOAT7 is also involved in fatty liver disease. Here we identified two novel homozygous variants in MBOAT7, NM_024298.5: c.1062C>A; p.(Tyr354*) and c.1135del; p.(Leu379Trpfs*9), in two unrelated Iranian families by means of whole exome sequencing. Sanger sequencing was performed to confirm the identified variants and also to investigate whether they co-segregate with the patients' phenotypes. To understand the functional consequences of these changes, we overexpressed recombinant wild type MBOAT7 and mutants in vitro and showed these mutations resulted in abolished protein synthesis and expression, indicating a complete loss of function. Albeit, we did not trace any liver diseases in our patients, but presence of globus pallidus signal changes in Magnetic Resonance Images might be indicative of metabolic changes as a result of loss of MBOAT7 expression in hepatic cells. These signal changes could also help as an important marker of MBOAT7 deficiency while analyzing the genomic data of patients with similar phenotypes.

膜结合的含有 O-酰基转移酶结构域的 7 ( MBOAT7 ) 基因编码一种参与调节溶血磷脂酰肌醇中花生四烯酸掺入的酶。MBOAT7纯合无义突变的患者患有智力障碍 (ID)，伴有癫痫和自闭症。从人类遗传研究中获得的越来越多的证据表明，MBOAT7也与脂肪肝疾病有关。在这里，我们在MBOAT7 中发现了两个新的纯合变体, NM_024298.5: c.1062C>A; p.(Tyr354*) 和 c.1135del；p.(Leu379Trpfs*9)，通过全外显子组测序在两个不相关的伊朗家族中。进行 Sanger 测序以确认已识别的变异，并调查它们是否与患者的表型共同分离。为了了解这些变化的功能后果，我们在体外过度表达了重组野生型MBOAT7和突变体，并表明这些突变导致蛋白质合成和表达消失，表明功能完全丧失。尽管我们没有追踪患者的任何肝脏疾病，但磁共振图像中苍白球信号变化的存在可能表明MBOAT7缺失导致的代谢变化在肝细胞中表达。在分析具有相似表型的患者的基因组数据时，这些信号变化也有助于作为MBOAT7缺乏症的重要标志物。