巴基斯坦语言障碍先证和家庭TM4SF20、NFXL1、CNTNAP2和ATP2C2罕见遗传变异研究

IF 0.8 Q4 GENETICS & HEREDITY
Erin M. Andres , HeatherL. Neely , Huma Hafeez , Tahira Yasmin , Farzana Kausar , M. Asim Raza Basra , Muhammad Hashim Raza
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引用次数: 3

摘要

语言障碍具有高度的遗传性和家族聚集性。LI的遗传调查揭示了许多感兴趣的染色体区域和基因,尽管很少有研究集中在非英语国家或非欧洲样本的罕见变异分析上。我们选择了四个候选基因(TM4SF20、NFXL1、CNTNAP2和ATP2C2)强烈提示与LI亚型特异性语言障碍(SLI)有关,并通过对来自巴基斯坦的LI先证进行Sanger测序,研究了罕见的蛋白质编码变异。先证者及其家庭成员完成了一份言语和语言家族史调查问卷,以及一份词汇量测试——皮博迪图片词汇测试第四版(PPVT-4),该测试被翻译成巴基斯坦的国语乌尔都语。我们的研究旨在通过在一个具有高亲缘关系的新人群中进行分离分析,确定这些SLI候选基因中罕见变异的意义。总的来说,我们确定了16个罕见变异(根据gnomAD v2.1.1数据库外显子组中全球人群中罕见的MAF),包括南亚人群中MAF为0.5%的8个变异。大多数鉴定出的罕见变异聚集在先证者的家族中,一个罕见变异(c.*9 T >C在CNTNAP2中)在一个小家庭(PKSLI-64)和另一个(C . 2465c >T在ATP2C2中)在先证者分支(pksl -27)中共分离。大多数已确定的罕见变异缺乏完全的共分离表明,虽然这些基因可能与LI的总体风险有关,但其他基因可能与该人群的LI有关。未来对这些近亲家庭的研究有可能扩大我们对与语言习得和语言障碍相关的基因功能的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment

Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions and genes of interest, though very few studies have focused on rare variant analysis in non-English speaking or non-European samples. We selected four candidate genes (TM4SF20, NFXL1, CNTNAP2 and ATP2C2) strongly suggested for specific language impairment (SLI), a subtype of LI, and investigated rare protein coding variants through Sanger sequencing of probands with LI ascertained from Pakistan. The probands and their family members completed a speech and language family history questionnaire and a vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, the national language of Pakistan. Our study aimed to determine the significance of rare variants in these SLI candidate genes through segregation analysis in a novel population with a high rate of consanguinity. In total, we identified 16 rare variants (according to the rare MAF in the global population in gnomAD v2.1.1 database exomes), including eight variants with a MAF <0.5% in the South Asian population. Most of the identified rare variants aggregated in proband's families, one rare variant (c.*9 T > C in CNTNAP2) co-segregated in a small family (PKSLI-64) and another (c.2465C > T in ATP2C2) co-segregated in the proband branch (PKSLI-27). The lack of complete co-segregation of most of the identified rare variants indicates that while these genes could be involved in the overall risk for LI, other genes are likely involved in LI in this population. Future investigation of these consanguineous families has the potential to expand our understanding of gene function related to language acquisition and impairment.

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来源期刊
Meta Gene
Meta Gene Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
1.10
自引率
0.00%
发文量
20
期刊介绍: Meta Gene publishes meta-analysis, polymorphism and population study papers that are relevant to both human and non-human species. Examples include but are not limited to: (Relevant to human specimens): 1Meta-Analysis Papers - statistical reviews of the published literature of human genetic variation (typically linked to medical conditionals and/or congenital diseases) 2Genome Wide Association Studies (GWAS) - examination of large patient cohorts to identify common genetic factors that influence health and disease 3Human Genetics Papers - original studies describing new data on genetic variation in smaller patient populations 4Genetic Case Reports - short communications describing novel and in formative genetic mutations or chromosomal aberrations (e.g., probands) in very small demographic groups (e.g., family or unique ethnic group). (Relevant to non-human specimens): 1Small Genome Papers - Analysis of genetic variation in organelle genomes (e.g., mitochondrial DNA) 2Microbiota Papers - Analysis of microbiological variation through analysis of DNA sequencing in different biological environments 3Ecological Diversity Papers - Geographical distribution of genetic diversity of zoological or botanical species.
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