Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Jie Zhang, Yaxin Huang, Yulei Hu, Bing Bai
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引用次数: 0

Abstract

Segawa syndrome is a rare autosomal recessive form of dopa-responsive dystonia resulting from TH gene dysfunction. Patients typically exhibit symptoms such as generalized dystonia, rigidity, tremors, infantile Parkinsonism, and pseudo-spastic paraplegia. Levodopa is often an effective treatment. Due to its rarity, high heterogeneity, and poorly understood pathological mutation and phenotype spectrums, as well as genotype–phenotype and genotype-treatment outcome correlations, Segawa syndrome poses diagnostic and therapeutic challenges. In our study, through clinical and molecular analyses of three Chinese Segawa patients, we re-evaluated the pathogenicity of a TH mutation (c.880G>C;p.G294R) previously categorized as “Conflicting classifications of pathogenicity” in ClinVar. Also, we summarized the clinical phenotypes of all reported Segawa syndrome cases until 2023 and compared them with our patients. We identified a novel phenotype, “cafe-au-lait macules,” not previously observed in Segawa patients. Additionally, we discussed the correlation between specific genotypes and phenotypes, as well as genotypes and treatment outcomes of our three cases. Our findings aim to enhance the understanding of Segawa syndrome, contributing to improved diagnosis and treatment approaches in the future.

Abstract Image

Abstract Image

三名中国濑川综合征患者的复合杂合突变及其治疗结果
濑川综合征是一种罕见的常染色体隐性遗传性多巴反应性肌张力障碍,由 TH 基因功能障碍引起。患者通常表现出全身肌张力障碍、僵直、震颤、小儿帕金森病和假性痉挛性截瘫等症状。左旋多巴通常是一种有效的治疗方法。由于其罕见性、高度异质性、对病理突变和表型谱以及基因型-表型和基因型-治疗结果之间的相关性知之甚少,濑川综合征给诊断和治疗带来了挑战。在我们的研究中,通过对三名中国濑川患者的临床和分子分析,我们重新评估了之前在 ClinVar 中被归类为 "致病性分类冲突 "的 TH 突变(c.880G>C;p.G294R)的致病性。此外,我们还总结了截至 2023 年所有报道的濑川综合征病例的临床表型,并与我们的患者进行了比较。我们发现了一种新的表型--"咖啡色黄斑",这是以前在濑川患者中未观察到的。此外,我们还讨论了特定基因型与表型之间的相关性,以及三个病例的基因型和治疗结果。我们的研究结果旨在加深人们对濑川综合征的了解,为今后改进诊断和治疗方法做出贡献。
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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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