两个巴基斯坦家庭中导致智力残疾的 HCFC1 和 MN1 基因变异。

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Syeda Iqra Hussain, Nazif Muhammad, Shahbaz Ali Shah, Adil U Rehman, Sher Alam Khan, Shamim Saleha, Yar Muhammad Khan, Noor Muhammad, Saadullah Khan, Naveed Wasif
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引用次数: 0

摘要

背景:智力障碍(ID)是一种神经发育疾病,影响着全球约 2% 的儿童和青少年,其特征是智力功能和适应行为的缺陷。遗传因素是导致 ID 表型形成的原因之一,包括染色体的突变和结构变化。HCFC1 基因的致病变异会导致 X 连锁智力低下综合征,又称 Siderius 型 X 连锁智力低下。MN1 基因是上颚发育所必需的,该基因突变会导致一种名为 CEBALID 综合征的遗传病:方法:利用外显子组测序鉴定了来自巴基斯坦不同地区的两个受影响家庭 A 和 B 的致病变体。这两个家族中的受影响个体均表现为智障、发育迟缓和行为异常。利用桑格测序法对筛选出的变体进行了验证和共分离分析:结果:在一个X连锁家族A中,发现了HCFC1基因(NM_005334.3)中的一个新型半杂合错义变异体(c.5705G > A; p.Ser1902Asn);而在家族B中,外显子组测序发现了MN1基因(NM_032581.4)外显子-1中的一个杂合无义变异体(c.3680 G > A; p.Trp1227Ter)。桑格(Sanger)测序证实了这些变异体在每个家庭中的ID分离:对两个巴基斯坦家庭的调查发现了 HCFC1 和 MN1 基因中的致病基因变异,这些变异可导致 ID 并扩大这些基因的变异谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.

Background: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome.

Methods: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing.

Results: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family.

Conclusions: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.

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来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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