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

Autor: Bardakov SN; S.M. Kirov Military Medical Academy, Saint Petersburg, Russia., Deev RV; North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia.; Human Stem Cells Institute, Moscow, Russia., Isaev АА; Human Stem Cells Institute, Moscow, Russia.; Genotarget LLC, Skolkovo Innovation Centre, Moscow, Russia., Khromov-Borisov NN; Almazov National Medical Research Centre, Saint Petersburg, Russia., Kopylov ED; North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia., Savchuk МR; North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia., Pushkin MS; North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia., Presnyakov EV; North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia., Magomedova RM; Dagestan State Medical University, Makhachkala, Russia., Achmedova PG; Dagestan State Medical University, Makhachkala, Russia., Umakhanova ZR; Dagestan State Medical University, Makhachkala, Russia., Kaimonov VS; Genetico, Moscow, Russia., Musatova EV; Genetico, Moscow, Russia., Blagodatskikh KА; Genetico, Moscow, Russia., Tveleneva AА; Genetico, Moscow, Russia., Sofronova YV; Genetico, Moscow, Russia., Yakovlev IA; Human Stem Cells Institute, Moscow, Russia.; Genotarget LLC, Skolkovo Innovation Centre, Moscow, Russia.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2023 Oct; Vol. 11 (10), pp. e2236. Date of Electronic Publication: 2023 Aug 08.
DOI: 10.1002/mgg3.2236
Abstrakt: 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).
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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