Algorithm for molecular diagnosis of hereditary pathology associated with single-gene CNVs
https://doi.org/10.25557/2073-7998.2022.11.36-39
Abstract
Single-gene copy number variations (CNVs) in patients with impaired psychomotor development are detected with a frequency of up to 10%. The outcome of this type of aberration is more obvious if a dosage-sensitive gene associated with the disease is affected. However, a pathological phenotype can also be formed as a result of hemizygotization of a recessive nucleotide sequence variant from an intact homologue or by combining CNV and a nucleotide variant (compound heterozygote). We have developed and tested for 1176 patients an algorithm for the molecular diagnosis of hereditary pathology associated with single-gene CNV. Pathogenic, likely pathogenic and structural chromosomal aberrations with uncertain clinical significance were detected in 478 probands (40.6%), including monogenic CNV in 60 patients (5.1%). Among 32 single-gene aberrations, the presence of which was confirmed by real-time PCR, most were inherited from healthy parents (23 CNV or 72%). Seven patients underwent sequencing. Not a single pathogenic nucleotide sequence variant was identified on the intact homologue, but in some cases, previously unreported variants of uncertain significance were found in genes not involved in CNV.
About the Authors
A. A. Kashevarova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
M. E. Lopatkina
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
O. Yu. Vasilyeva
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
D. A. Fedotov
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
E. A. Fonova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
A. A. Sivtsev
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
A. A. Zarubin
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
I. N. Lebedev
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
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Review
For citations:
Kashevarova A.A., Lopatkina M.E., Vasilyeva O.Yu., Fedotov D.A., Fonova E.A., Sivtsev A.A., Zarubin A.A., Lebedev I.N. Algorithm for molecular diagnosis of hereditary pathology associated with single-gene CNVs. Medical Genetics. 2022;21(11):36-39. (In Russ.) https://doi.org/10.25557/2073-7998.2022.11.36-39
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