Exome-based search for recurrent disease-causing alleles in Russian population

Grigoriy A. Yanus, Tatiana A. Akhapkina, Aldon J. Whitehead, Ilya V. Bizin, Aglaya G. Iyevleva, Ekaterina Sh Kuligina, Svetlana N. Aleksakhina, Maria O. Anisimova, Maxim M. Holmatov, Alexandr A. Romanko, Olga A. Zaitseva, Olga S. Yatsuk, Kirill A. Zagorodnev, Maria A. Matsneva, Andrey V. Koloskov, Alexandr V. Togo, Evgeny N. Suspitsin, Evgeny N. Imyanitov

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7 Scopus citations


Exomes of 27 Russian subjects were analyzed for the presence of medically relevant alleles, such as protein-truncating variants (PTVs) in known recessive disease-associated genes and pathogenic missense mutations included in the ClinVar database. 36 variants (24 PTVs and 12 amino acid substitutions) were identified and then subjected to the analysis in 897 population controls. 9/36 mutations were novel, however only two of them (POLH c.490delG associated with xeroderma pigmentosum variant (XPV) and CATSPER1 c.859_860delCA responsible for spermatogenic failure) were shown to be recurrent. 27 out of 36 pathogenic alleles were already described in prior genetic studies; seven of them occurred only in the index cases, while 20 demonstrated evidence for persistence in Russian population. In particular, non-random occurrence was revealed for SERPINA1 c.1096G > A (alpha-1 antitrypsin deficiency), C8B c.1282C > T and c.1653G > A (complement component 8B deficiency), ATP7B c.3207C > A (Wilson disease), PROP1 c.301_302delAG (combined pituitary hormone deficiency), CYP21A2 c.844G > T (non-classical form of adrenogenital syndrome), EYS c.1155T > A (retinitis pigmentosa), HADHA c.1528G > C (LCHAD deficiency), SCO2 c.418G > A (cytochrome c oxidase deficiency), OTOA c.2359G > T (sensorineural deafness), C2 c.839_866del (complement component 2 deficiency), ACADVL c.848T > C (VLCAD deficiency), TGM5 c.337G > T (acral peeling skin syndrome) and VWF c.2561 G > A (von Willebrand disease, type 2N). These data deserve to be considered in future medical genetic activities.

Original languageEnglish
Article number103656
JournalEuropean Journal of Medical Genetics
Issue number7
StatePublished - Jul 2019
Externally publishedYes


  • Founder effect
  • Germ-line mutation
  • Heterozygote screening
  • Recessive genetic conditions
  • Whole exome sequencing (WES)


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