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

Theberge, E. T.; Durbano, K.; Demailly, D.; Huby, S.; Mohajeri, A.; Care4Rare Canada Consortium, ; van Karnebeek, C.; Horvath, G. A.; Usdin, K.; Lehman, A.; Cif, L.; Richmond, P. A.

2024-06-05 neurology
10.1101/2024.06.05.24308127 medRxiv
Show abstract

BackgroundTrinucleotide 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. ObjectivesTo identify the genetic cause of a severe progressive movement disorder phenotype in two affected brothers. MethodsA 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). ConclusionsThis is the first report of a severe progressive movement disorder phenotype attributed to a CGG repeat expansion in the DIP2B 5-UTR.

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