DIP2B CGG repeat expansion in siblings with neurodevelopmental disability and progressive movement disorder

Background Trinucleotide repeat expansions are an emerging class of genetic variants associated with several movement disorders. Unbiased genome-wide analyses can reveal novel genotype-phenotype associations and provide a diagnosis for patients and families. Objectives To identify the genetic cause of a severe progressive movement disorder phenotype in two affected brothers. Methods A family of two affected brothers and unaffected parents had extensive phenotyping and natural history followed since birth. Whole-genome and long-read sequencing methods were used to characterize genetic variants and methylation status. Results: We describe a CGG repeat expansion in the 5’-untranslated region of DIP2B in two affected male siblings presenting with a novel DIP2B phenotype including neurodevelopmental disability, dysmorphic traits, and a severe progressive movement disorder (prominent chorea, dystonia, and ataxia). Conclusions This is the first report of a severe progressive movement disorder phenotype attributed to a CGG repeat expansion in the DIP2B 5’-UTR.