CCDC88C中一个新的c.3636-4 A>G突变在家族性脊髓小脑共济失调中起致病作用。

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2023-01-01 Epub Date: 2023-10-27 DOI:10.1159/000534692
Senmao Chai, Deyang Liu, Yajing Liu, Ming Sang
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引用次数: 0

摘要

简介:脊髓角性共济失调(SCA)是一种以小脑神经功能缺损为特征的常染色体显性遗传疾病。具体而言,其主要临床表现为共济失调伴周围神经损伤。共鉴定出48个SCA致病基因。本研究旨在鉴定一个由八个患病个体组成的四代中国家族中常染色体显性SCA的致病基因。方法:从家系成员中提取基因组DNA样本,进行基因组全外显子组测序(WES),然后进行双向Sanger测序和小基因分析以鉴定突变位点。结果:在四个受影响的成员中,在含有88C(CCDC88C)基因的卷曲螺旋结构域的剪接区发现了一个新的致病性杂合突变(NM_001080414:c.3636-4 A>G)。CCDC88C基因突变导致SCA40(OMIM:616053),这是一种罕见的儿童期无症状SCA亚型。我们的研究结果进一步证明了CCDC88C基因在SCA中的作用,并表明CCDC88C的c.3636-4 A>G(NM_001080414)变体是SCA40晚发表型的原因。我们的发现丰富了CCDC88C基因的突变谱,为SCA40的遗传咨询提供了理论依据。
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A Novel c.3636-4 A>G Mutation in the CCDC88C Plays a Causative Role in Familial Spinocerebellar Ataxia.

Introduction: Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprising eight affected individuals.

Methods: Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites.

Results: A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (CCDC88C) gene (NM_001080414:c.3636-4 A>G) was identified in four affected members. The minigene assay results indicated that this mutation leads to the insertion of CAG bases (c.3636-1_3636-3 insCAG).

Conclusion: CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of CCDC88C gene and provide a theoretical basis for the genetic counseling of SCA40.

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来源期刊
Human Heredity
Human Heredity 生物-遗传学
CiteScore
2.50
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.
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