Abstract
OBJECTIVES: Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (IDDSADF) is caused by heterozygous CNOT3 (MIM# 604910) variants on chromosome 19q13. This study aimed to identify and describe the clinical features of a Korean family with maternally inherited speech delay and intellectual and developmental disability to elucidate the underlying genetic mechanism. METHODS: We conducted whole-exome sequencing and confirmatory Sanger sequencing on the proband, the mother, and unaffected grandparents with wild-type genotypes. RESULTS: The phenotypes of the mother and 2 daughters presented muscular hypotonia, global developmental delay, speech delay, intellectual disability, macrocephaly, facial dysmorphic features, and focal corpus callosum hypoplasia. Whole-exome sequencing identified a novel in-frame deletion, c.2017_2019del (p.Phe673del) in CNOT3, located in the C-terminal negative on the TATA-less-box domain. DISCUSSION: This report presents a new possible mechanism underlying IDDSADF caused by CNOT3 variants-an in-frame deletion. The findings enhance our understanding of early-life neurodevelopment and the genotype-phenotype relationships of IDDSADF caused by CNOT3 variants. In addition, this report could assist in early diagnosis and facilitate genetic counseling.