对达吉斯坦共和国一个与世隔绝的山区人群中DYSF基因的一种地方性突变进行基因筛查。

Genetic screening of an endemic mutation in the DYSF gene in an isolated, mountainous population in the Republic of Dagestan.

作者信息

Bardakov Sergey N, Deev Roman V, Isaev Аrtur А, Khromov-Borisov Nikita N, Kopylov Evgeniy D, Savchuk Мaria R, Pushkin Maxim S, Presnyakov Evgeniy V, Magomedova Raisat M, Achmedova Patimat G, Umakhanova Zoya R, Kaimonov Vladimir S, Musatova Elizaveta V, Blagodatskikh Konstantin А, Tveleneva Aleksandra А, Sofronova Yana V, Yakovlev Ivan A

机构信息

S.M. Kirov Military Medical Academy, Saint Petersburg, Russia.

North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia.

出版信息

Mol Genet Genomic Med. 2023 Oct;11(10):e2236. doi: 10.1002/mgg3.2236. Epub 2023 Aug 8.

DOI:10.1002/mgg3.2236

PMID:37553796

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10568376/

Abstract

BACKGROUND

Dysferlinopathy has a high prevalence in relatively isolated ethnic groups where consanguineous marriages are characteristic and/or the founder effect exists. However, the frequency of endemic mutations in most isolates has not been investigated.

METHODS

The prevalence of the pathological DYSF gene variant (NM_003494.4); c.200_201delinsAT, p. Val67Asp (rs121908957) was investigated in an isolated Avar population in the Republic of Dagestan. Genetic screenings were conducted in a remote mountainous region characterized by a high level of consanguinity among its inhabitants. In total, 746 individuals were included in the screenings.

RESULTS

This pathological DYSF gene variant causes two primary phenotypes of dysferlinopathy: limb-girdle muscular dystrophy (LGMD) type R2 and Miyoshi muscular dystrophy type 1. Results indicated a high prevalence of the allele at 14% (95% confidence interval [CI]: 12-17; 138 out of 1518 alleles), while the allele in the homozygous state was detected in 29 cases-3.8% (CI: 2.6-5.4). The population load for dysferlinopathy was 832.3 ± 153.9 per 100,000 with an average prevalence of limb-girdle muscular dystrophies ranging from 0.38 ± 0.38 to 5.93 ± 1.44 per 100,000.

CONCLUSION

A significant burden of the allele was due to inbreeding, as evidenced by a deficiency of heterozygotes and the Wright fixation index equal to 0.14 (CI 0.06-0.23).

摘要

背景

在近亲结婚具有特征性和/或存在奠基者效应的相对隔离的族群中，dysferlinopathy的患病率较高。然而，大多数隔离群体中地方性突变的频率尚未得到研究。

方法

在达吉斯坦共和国一个隔离的阿瓦尔人群中，对病理性DYSF基因变异（NM_003494.4）；c.200_201delinsAT，p.Val67Asp（rs121908957）的患病率进行了调查。在一个偏远山区进行了基因筛查，该地区居民的近亲结婚程度很高。总共有746人参与了筛查。

结果

这种病理性DYSF基因变异导致dysferlinopathy的两种主要表型：R2型肢带型肌营养不良（LGMD）和1型宫下型肌营养不良。结果表明，该等位基因的患病率较高，为14%（95%置信区间[CI]：12 - 17；1518个等位基因中有138个），而纯合状态的等位基因在29例中被检测到，占3.8%（CI：2.6 - 5.4）。dysferlinopathy的人群负荷为每10万人832.3±153.9，肢带型肌营养不良的平均患病率为每10万人0.38±0.38至5.93±1.44。