Risk-based analysis of test panels for carrier screening for monogenic disorders


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Abstract

A number of autosomal recessive diseases with well-known genetic markers are relatively common in the Russian Federation. The diagnostic effectiveness of test panels is traditionally based on the prevalence of determinable mutations, which is rather difficult to detect in heterogeneous populations. Objective: To evaluate the effectiveness of the screening panel for carriage of CFTR gene mutations in the Russian Federation using a risk-based approach. Materials and methods: Molecular genetic testing of blood samples of 1000 healthy donors was carried out by analyzing the 24 most frequent mutations in the CFTR gene using the real-time PCR with the analysis of melting profile. Results: The study found out 29 mutation carriers among 1000 healthy individuals. The total prevalence of detectable mutations was 2.9%. The vulnerability of the panel with a 95% probability is no more than 31%, which is close enough to the value of the vulnerability theoretically calculated basing on the prevalence of the mutations included (24.5). When using this panel (with the carriage of mutations in the CFTR gene), the risk of having an affected child in both partners will be only 1/170068, which is 17 times lower than the general population risk. Conclusion: Use of this screening panel in both partners may reduce the risk of affected offspring by 17 times, compared to the general population risk. Using a risk-based approach allowed us to effectively evaluate the vulnerability of the panel. If the incidence of the disease is known, this technique is applicable for any heterogeneous population.

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About the authors

Gaukhar Yu. Zobkova

Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia

Email: zobkova.dna@gmail.com
PhD student at the Department of Medical Genetics

Andrew E. Donnikov

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: a_donnikov@oparina4.ru
Ph.D., Head of the Laboratory of Molecular Genetic Methods

Alexander N. Prytkov

Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia

PhD., Associate Professor, Senior Researcher at the Department of Medical Genetics

Natalia S. Demikova

Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia

Dr. Med. Sci., Professor, Head of the Department of Medical Genetics

Aligeidar A. Ragimov

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: ra50@mail.ru
Dr. Med. Sci., Professor, Head of the Department of Intensive Care and Anesthesiology

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