Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children14310.24287/1726-1708-2016-15-1-10-16ИММУНОЛОГИЯMolecular genetic diagnosis of primary immunodeficiencies (Review of literature and clinical case reports)Молекулярно-генетическая диагностика первичных иммунодефицитных состояний (обзор литературы и собственные клинические наблюдения)KuzmenkoNatalya B.КузьменкоНаталья Борисовна
Russian Federation
plunge@list.ruVarlamovaTatyana V.ВарламоваТатьяна Владимировна
Russian Federation
imers@mail.ruMersiyanovaIrina V.МерсияноваИрина Викторовна
Russian Federation
imers@mail.ruRaikinaElena V.РайкинаЕлена Владиславовна
Russian Federation
e_raikina@inbox.ruBobryninaVlasta O.БобрынинаВласта Олеговна
Russian Federation
vlastabobrynina@yandex.ruShcherbinaAnna Yu.ЩербинаАнна Юрьевна
Russian Federation
shcher26@hotmail.comFederal Research Center of Pediatric Hematology, Oncology, and Immunology named after Dmitry RogachevФедеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава РоссииZAO “Genoanalytica”ЗАО «Геноаналитика»19032016151101619092018Copyright ©; 2016, «D. Rogachev NMRCPHOI»Copyright ©; 2016, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2016«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/143

Primary immunodeficiencies (PIDs) form a heterogeneous group of diseases associated with high incidence of infections, autoimmune diseases and malignancies. About 300 genes are known, breakage in which lead to immunodeficiency. Understanding of the mechanisms of inheritance of PID, their characteristics, and the external factors essential for manifestation of the genetic defects makes it possible to predict the clinical manifestations of immunodeficiency at the early stages of diagnosis, determines the treatment strategy, and predicts the probability of healthy progeny in families with a history of the disease. Clinical case reports from the authors' practice illustrate various regularities and phenomena of PIDs inheritance. Sixteen embryos of siblings with genetically determined PID were examined for prenatal diagnosis. The diagnosis of PIDs was confirmed in 4 of 16 embryos. Recommendations on examinations of relatives of patients with PIDs are presented in the article.

первичные иммунодефицитные состояниямолекулярно-генетическая диагностикамеханизмы наследованияпренатальная диагностикаprimary immunodeficienciesmolecular genetic diagnosismechanisms of inheritanceprenatal diagnosisAl-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. Front Immunol. 2014; 5: 162.Fischer A. Human primary immunodeficiency diseases. Immunity. 2007; 27(6): 835-45.Pessia E, Makino T, Bailly-Bechet M, McLysaght A, Marais GA. Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome. Proc Natl Acad Sci USA. 2012; 109(14): 5346-51.Nguyen DK, Disteche CM. Dosage compensation of the active X chromosome in mammals. Nat Genet. 2006; 38(1): 47-53.Rösen-Wolff A, Soldan W, Heyne K, Bickhardt J, Gahr M, Roesler J. Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization. Ann Hematol. 2001; 80(2): 113-5.Moellering RC Jr, Weinberg AN. Persistent Salmonella infection in a female carrier for chronic granulomatous disease. Ann Intern Med. 1970; 73(4): 595-601.Miyazaki S, Shin H, Goya N, Nakagawara A. Identification of a carrier mother of a female patient with chronic granulomatous disease. J Pediatr. 1976; 89(5): 784-6.Mills EL, Rholl KS, Quie PG. X-linked inheritance in females with chronic granulomatous disease. J Clin Invest. 1980; 66(2): 332-40.Lun A, Roesler J, Renz H. Unusual late onset of X-linked chronic granulomatous disease in an adult woman after unsuspicious childhood. Clin Chem. 2002; 48(5): 780-1.Dusi S, Poli G, Berton G, Catalano P, Fornasa CV, Peserico A. Chronic granulomatous disease in an adult female with granulomatous cheilitis. Evidence for an X-linked pattern of inheritance with extreme lyonization. Acta Haematol. 1990; 84(1): 49-56.Curnutte JT, Hopkins PJ, Kuhl W, Beutler E. Studying X inactivation. Lancet. 1992; 339(8795): 749.Al-Herz W, Aldhekri H, Barbouche MR, Rezaei N. Consanguinity and primary immunodeficiencies. Hum Hered. 2014; 77(1-4): 138-43.Rezaei N, Mohammadinejad P, Aghamohammadi A. The demographics of primary immunodeficiency diseases across the unique ethnic groups in Iran, and approaches to diagnosis and treatment. Ann N Y Acad Sci. 2011; 1238: 24-32.Varon R, Seemanova E, Chrzanowska K, Hnateyko O, Piekutowska-Abramczuk D, Krajewska-Walasek M, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet. 2000; 8(11): 900-2.Martlnez-Feito A, Melero J, Mora-DIaz S, Rodrlguez-Vigil C, Elduayen R, Gonzalez-Granado LI, et al. Autoimmune lymphoproliferative syndrome due to somatic FAS mutation (ALPS-sFAS) combined with a germline caspase-10 (CASP10) variation. Immunobiology. 2016; 221(1): 40-7.Borregaard N. Severe congenital neutropenia: new lane for ELANE. Blood. 2014: 123(4): 462-3.Ochs HD, Smith CIE, Puck J.M., eds. Primary immunodeficiency diseases: a molecular and genetic approach. 2nd ed. Oxford University Press: 2007: Pt 2.Zhu Q, Zhang M, Blaese RM, Derry JM, Junker A, Francke U, et al. The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene. Blood. 1995; 86(10): 3797-804. Available at: http: //www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/pubmed/7579347Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol. 2008; 15(1): 30-6.Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N. Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant. 2009; 15(1, Suppl): 84-90.Ochs HD, Smith CIE, Puck JM., eds. Primary immunodeficiency diseases: a molecular and genetic approach. 2nd ed. Oxford University Press: 2007: Pt 1: 16-9.Biesecker LG, Spinner NB. A genomic view of mosaicism and human disease. Nat Rev Genet. 2013; 14(5): 307-20.