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

IF 7.6 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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迪斯科相互作用蛋白2同源物B - CGG重复扩增与神经发育障碍和进行性运动障碍的兄弟姐妹。

背景：三核苷酸重复扩增是一类新兴的与各种运动障碍相关的遗传变异。无偏倚的全基因组分析可以揭示新的基因型-表型关联，并为患者和家庭提供诊断。目的：目的是确定遗传原因严重进行性运动障碍表型在2个受影响的兄弟。方法：一个有2个患病兄弟和未患病父母的家庭，自出生以来有广泛的表型。全基因组和长读测序方法表征了遗传变异和甲基化状态。结果：两名男性兄弟姐妹在迪科相互作用蛋白2同源物B （DIP2B）的5'-非翻译区（UTR）存在CGG重复扩增，表现出一种新的DIP2B表型，包括神经发育障碍、畸形特征和严重的进行性运动障碍（舞蹈病、肌张力障碍和共济失调）。结论：这是首次报道与DIP2B 5'-UTR中CGG重复扩增相关的严重进行性运动障碍表型。©2025国际帕金森和运动障碍学会。这篇文章是由美国政府雇员贡献的，他们的工作在美国属于公有领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.