Molecular Characteristics, Clinical and Immunologic Manifestations of 11 Children with Omenn Syndrome in East Slavs (Russia, Belarus, Ukraine).

Autor: Sharapova SO; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, v. Borovliani, Frunzenskaja str., 223053, Minsk, Belarus. sharapovasv@gmail.com., Guryanova IE; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, v. Borovliani, Frunzenskaja str., 223053, Minsk, Belarus., Pashchenko OE; Department of Clinical Immunology, Russian Clinical Children's Hospital, Moscow, Russia., Kondratenko IV; Department of Clinical Immunology, Russian Clinical Children's Hospital, Moscow, Russia., Kostyuchenko LV; West-Ukrainian Children's Medical Center, Lvov, Ukraine., Rodina YA; Department of Immunology, Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russia., Varlamova TV; Department of Immunology, Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russia., Bondarenko AV; Department of Pediatric Infectious Diseases and Immunology, Medical Academy of Postgraduate Education, Kiev, Ukraine., Chernyshova LI; Department of Immunology, Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russia., Gyseva MN; Consulting Center of Pediatric Medical Academy, St. Petersburg, Russia., Belevtsev MV; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, v. Borovliani, Frunzenskaja str., 223053, Minsk, Belarus., Minakovskaya NV; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, v. Borovliani, Frunzenskaja str., 223053, Minsk, Belarus., Aleinikova OV; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, v. Borovliani, Frunzenskaja str., 223053, Minsk, Belarus.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2016 Jan; Vol. 36 (1), pp. 46-55. Date of Electronic Publication: 2015 Nov 23.
DOI: 10.1007/s10875-015-0216-7
Abstrakt: Background: Omenn syndrome [Mendelian Inheritance (OMIM 603554)] is a genetic disease of the immune system, characterized by the presence of fatal generalized severe erythroderma, lymphoadenopathy, eosinophilia and profound immunodeficiency.
Objective: We studied clinical and immunologic presentation of the disease manifestation among East Slavs population with genetically confirmed Omenn syndrome.
Results: We collected clinical and immunologic data of 11 patients (1 from Belarus, 5--Ukraine, 5--Russia): 6 females, 5 males. The age of Omenn syndrome manifestation varied from the 1st day of life to 1 year and 1 month, the age of diagnosis--20 days to 1 year and 10 months. Nine out of 11 patients had classic immunologic phenotype T(+/-)B-NK+, 1 pt had TlowB + NK+ with CD3 + TCRgd + expansion and 1 had TlowB+/-NK+ phenotype. Eight out of 11 pts had mutation in RAG1 gene, 4 out of 8 had c.368-369delAA (p.K86fsX118) in homozygous state or heterozygous compound. In our cohort of patients, we also described two new mutations in RAG genes (p.E722Q in RAG1 and p.M459R in RAG2). At present, 7/11 were transplanted and 5 out of the transplanted are alive.
Conclusion: This study demonstrates that the most popular genetic abnormality in East Slavs children with Omenn syndrome is c.368-369delAA (p.K86fs118) in RAG1 gene, which may be connected with more favorable prognosis because 4/4 patients survived after hematopoietic stem cells transplantation.
Databáze: MEDLINE
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