Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.

在患有严重发育迟缓，智力残疾和癫痫病的患者中已经描述了TRIM8基因的突变。迄今为止仅描述了六例患者。所有先前的突变都是截短的变体，聚集在蛋白质的C末端。据报道，先前有TRIM8相关的癫痫性脑病患者患有肾病综合征。在这里，我们描述了一名8岁男性TRIM8患者的临床，影像学和组织学特征与以前的患者相比，该突变仅具有轻度智力障碍和良好控制的癫痫病。发现该患者2岁时患有蛋白尿。肾脏活检结果提示局灶性节段性肾小球硬化。他的肾功能下降，从5岁开始腹膜透析。他在7岁时接受了肾脏移植。基于三重奏的全基因组测序在TRIM8（NM_030912.2）c.1198_1220del，p。（Tyr400ArgfsTer2）中鉴定了一个新的从头杂合移码突变。该患者进一步证明TRIM8突变会导致神经和肾脏特征的综合症。我们的发现表明TRIM8的光谱与神经相关的疾病可能比以前认为的更广泛，可能伴有轻度的神经发育问题和/或更严重的进行性肾表型。我们强调了在TRIM8突变患者中需要进行蛋白尿筛查。