Heterozygous variants in CLTC, which encode the clathrin heavy chain protein, cause neurodevelopmental delay of varying severity, and often accompanied by dysmorphic features, seizures, hypotonia, and ataxia. To date, 28 affected individuals with CLTC variants have been reported, although their phenotypes have not been fully elucidated. Here, we report three novel de novo CLTC (NM_001288653.1) variants in three individuals with previously unreported clinical symptoms: c.3662_3664del:p.(Leu1221del) in individual 1, c.2878T>C:p.(Trp960Arg) in individual 2, and c.2430+1G>T:p.(Glu769_Lys810del) in individual 3. Consistent with previous reports, individuals with missense or small in-frame variants were more severely affected. Unreported symptoms included a brain defect (cystic lesions along the lateral ventricles of the brain in individuals 1 and 3), kidney findings (high-echogenic kidneys in individual 1 and agenesis of the left kidney and right vesicoureteral reflux in individual 3), respiratory abnormality (recurrent pneumonia in individual 1), and abnormal hematological findings (anemia in individual 1 and pancytopenia in individual 3). Of note, individual 1 even exhibited prenatal abnormality (fetal growth restriction, cystic brain lesions, high-echogenic kidneys, and a heart defect), suggesting that CLTC variants should be considered when abnormal prenatal findings in multiple organs are detected.

CLTC中的杂合变异体编码网格蛋白重链蛋白，导致不同严重程度的神经发育迟缓，并经常伴有畸形特征、癫痫发作、肌张力减退和共济失调。迄今为止，已报告了 28 名患有CLTC变异的受影响个体，尽管他们的表型尚未完全阐明。在这里，我们报告了三部新的从头CLTC(NM_001288653.1) 三个具有先前未报告的临床症状的个体的变异：个体 1 中的 c.3662_3664del:p.(Leu1221del)，个体 2 中的 c.2878T>C:p.(Trp960Arg)，以及个体 2 中的 c.2430+1G> T:p.(Glu769_Lys810del) 在个体 3 中。与之前的报告一致，具有错义或小的框内变异的个体受到更严重的影响。未报告的症状包括脑缺陷（个体 1 和 3 的大脑侧脑室囊性病变）、肾脏发现（个体 1 的高回声肾脏和个体 3 的左肾发育不全和右膀胱输尿管反流）、呼吸异常（个体 1 的复发性肺炎）和异常的血液学检查结果（个体 1 的贫血和个体 3 的全血细胞减少症）。值得注意的是，当检测到多个器官的异常产前发现时，应考虑CLTC变异。