突尼斯六个非亲缘关系家庭中与复发性 POLR3A 基因突变有关的震颤共济失调伴中枢骨髓抑制表型

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Ichraf Kraoua, Maha Jamoussi, Cyrine Drissi, Lilia Kraoua, Séverine Drunat, Hanene Benrhouma, Thouraya Ben Younes, Sonia Nagi, Sonia Abdelhak, Odile Boespflug Tanguy, Ilhem Ben Youssef-Turki, Mediha Trabelsi, Imen Dorboz
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引用次数: 0

摘要

背景:POLIII相关性白质营养不良症是最近被确认的一组遗传性白质疾病,具有相似的临床和放射学表型。突尼斯尚未发表过关于POLR3A变体导致的POLIII相关白质营养不良症的研究。本研究旨在对突尼斯队列中与 POLR3A 相关的白质营养不良症的临床、放射学和遗传学特征做出贡献:我们报告了 6 例经遗传学证实的 POLR3A 相关白营养不良症病例,分别属于 6 个无血缘关系的突尼斯家庭,并回顾了之前发表的儿科病例:所有患者均为近亲结婚,来自突尼斯北部或中部。发病年龄在 15 个月到 6 岁之间。所有患者的临床表型相似,主要特征为小脑共济失调、震颤和眼球震颤。脑成像显示,所有患者均存在弥漫性骨髓营养不良,其中三名患者存在进行性小脑萎缩。分子分析在所有患者的 POLR3A 基因中发现了相同的双等位基因 NM_007055.4:c.2011T>C;p.(Trp671Arg)变异:鉴于该变异在六个临床表型相似的非亲缘个体中再次出现,我们推测该变异具有创始人效应。鉴于突尼斯 POLR3A 患者的基因具有明显的同质性,复发变异体应被直接锁定。这将有助于指数患者的诊断和遗传咨询。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families.

Background: POLIII-related leukodystrophies are a group of recently recognized hereditary white matter diseases with a similar clinical and radiological phenotype. No Tunisian studies have been published about POLIII-related leukodystrophy due to POLR3A variants. The aim of this study was to contribute to the clinical, radiological, and genetic characterization of POLR3A-related leukodystrophy in a Tunisian cohort.

Methods: We report six cases of genetically confirmed POLR3A-related leukodystrophy belonging to six unrelated Tunisian families, along with a review of previously published pediatric cases.

Results: All patients were born to consanguineous marriages and originated from the North or the Center of Tunisia. Age at onset varied between 15 months and 6 years. The clinical phenotype was similar in all patients with cerebellar ataxia, tremor, and nystagmus being the key features. Brain imaging showed diffuse hypomyelination in all patients with progressive cerebellar atrophy in three patients. Molecular analysis identified the same bi-allelic NM_007055.4:c.2011T>C; p.(Trp671Arg) variant in the POLR3A gene in all patients.

Conclusion: We hypothesize a founder effect for the identified variant given its recurrence in six unrelated individuals with a similar clinical phenotype. Given the apparent genetic homogeneity of Tunisian POLR3A patients, the recurrent variant should be directly targeted. This should facilitate diagnosis in index patients, and genetic counseling.

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来源期刊
Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.20
自引率
0.00%
发文量
241
审稿时长
14 weeks
期刊介绍: Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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