Vissers‐Bodmer syndrome caused by a novel de novo CNOT1 frameshift variant

Abstract

AbstractVissers‐Bodmer Syndrome (VIBOS) is an autosomal dominant disorder caused by variants in the CNOT1 gene. It is characterized by systemic developmental and language‐motor delay, intellectual disabilities, growth and behavioral abnormalities, hypotonia, and distal skeletal defects, such as deformities of the hands and feet. This syndrome becomes evident during infancy and can display a highly variable phenotype. Thirty‐nine individuals with heterozygous de novo CNOT1 variants were first reported in 2019. Herein, we report a child with VIBOS who exhibited delayed motor development for over 4 years, along with hypotonia and atypical facial features. Notably, the patient developed short stature as the primary characteristic without any intellectual disability or organic nervous system lesions. Genetic testing revealed a de novo base duplication variant in exon 5 of the CNOT1 gene, NM_016284.5(CNOT1):c.316_317dup(p.Pro107Serfs*10). Importantly, the pathogenicity of this specific variant has not been reported in relevant literature. This study reports a new variant, thereby enriching the variant spectrum of CNOT1 associated with VIBOS, and contributes to the genetic counseling of affected families.