Disco-Interacting Protein 2 Homolog B CGG Repeat Expansion in Siblings with Neurodevelopmental Disability and Progressive Movement Disorder

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-01-24 DOI:10.1002/mds.30101

Emilie T. Théberge MSc, Kate Durbano MD, Diane Demailly MD, Sophie Huby MD, Aleksandra Mitina PhD, Yue Yin MSc, Arezoo Mohajeri MSc, Care4Rare Canada Consortium, Clara van Karnebeek MD, PhD, Gabriella A. Horvath MD, PhD, Ryan K.C. Yuen PhD, Karen Usdin PhD, Anna Lehman MD, Laura Cif MD, PhD, Phillip A. Richmond PhD

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Abstract

Background

Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome-wide analyses can reveal novel genotype–phenotype associations and provide a diagnosis for patients and families.

Objective

The aim was to identify the genetic cause of a severe progressive movement disorder phenotype in 2 affected brothers.

Methods

A family of 2 affected brothers and unaffected parents had extensive phenotyping since birth. Whole-genome and long-read sequencing methods characterized genetic variants and methylation status.

Results

Two male siblings with a CGG repeat expansion in the 5′-untranslated region (UTR) of disco-interacting protein 2 homolog B (DIP2B) presented with a novel DIP2B phenotype, including neurodevelopmental disability, dysmorphic traits, and a severe progressive movement disorder (chorea, dystonia, and ataxia).

Conclusions

This is the first report of a severe progressive movement disorder phenotype associated with a CGG repeat expansion in the DIP2B 5′-UTR. © 2025 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.