IMPE Abstracts

Purpose: Vissers-Bodmer Syndrome is an autosomal dominant disorder caused by CNOT1 gene mutation. It is characterized by systemic developmental delay, mental retardation, language-motor retardation, behavioral abnormalities, growth abnormalities, hypotonia, and distal skeletal defects such as deformities of the hands and feet, It’s evident from infancy. The phenotype is highly variable, with some people having only mild learning difficulties and others having severe cognitive impairment in their 50s. At present, reports about this disease are very rare. This paper reports this case of Vissers-Bodmer Syndrome in order to further improve the understanding of this disease.

Methods: We analyzed the clinical data and genetic test results of the case of Vissers-Bodmer Syndrome in the Second Xiangya Hospital of Central South University in January 2022 and summarized the clinical characteristics.

Results: The main manifestations of the proband were short stature, motor retardation, hypotonia, wide eye distance, narrow eyelid cleft, epicanthus, low ear, pronation of the nostril, short finger, etc. The clinical manifestations were consistent with Vissers-Bodmer syndrome. The whole exome was sequenced by targeted capture-high throughput sequencing, and the result showed repeated mutations of 316-317 bases in exon 5 of the encoding region of CNOT1 gene in the proband. This mutation is a frameshift mutation, which is in line with the suspected pathogenic mutation. The mutation site has not been reported in relevant literature. Neither of the proband's parents had the mutation, and the proband had heterozygous denovo mutation, which was consistent with the pathogenesis of autosomal dominant inheritance (AD) disease.

Conclusions: This study presents a rare case of CNOT1-driven Vissers-Bodmer Syndrome identifying a novel heterozygous frameshift variant of CNOT1(c.316_317dup). Our findings enrich the CNOT1 mutational spectrum and emphasize the importance of genetic testing in patients with microcephaly and short stature, motor retardation, dystonia, and special facial features. The pathophysiological mechanism of this new developmental disorder needs to be further studied.