title: Mutation c.256_257delAA in RAG1 Gene in Polish Children with Severe Combined Immunodeficiency: Diversity of Clinical Manifestations.
abstract: Mutations in RAG1 gene may result in different types of severe combined immunodeficiencies. In this study, we compare clinical symptoms and laboratory findings in four children with identical mutation in RAG1 gene. All of analyzed patients presented symptoms of severe combined immunodeficiencies associated or not with Omenn syndrome (OS) features. In our patients two different types of variants in RAG1 gene were detected. The first of the mutation was the deletion of AA dinucleotide at position c.256_257 (p.Lys86ValfsTer33), the second gene variant was substitution c.2867T>C (p.Ile956Thr). In Patient 1 we detected that compound heterozygous mutations involved both of the mentioned variants. Whereas, in Patients 2, 3 and 4, we confirmed the presence of the dinucleotide deletion but in a homozygous state. In all described patients, sequence analysis of RAG2 gene did not reveal any nucleotide changes. Our data show that mutation c.256_257delAA in RAG1 gene seems to occur quite frequently in the polish patients with severe combined immunodeficiency and may result in classical OS as well as in severe combined immunodeficiency without clinical and laboratory features of OS when occurred in homozygous state. The same mutation but in heterozygous state, in combination with other mutation in RAG1 gene, may result in incomplete OS.
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.|Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szaflarska
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.|Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rutkowska-Zapała
authors.affiliation: Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kotula
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gruca
authors.affiliation: Department of Medical Genetics, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, Krakow, Poland.|Department of Medical Genetics, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grabowska
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.|Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Lenart
authors.affiliation: Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Surman
authors.affiliation: Department of Transplantation, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, Krakow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Trzyna
authors.affiliation: Department of Transplantation, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, Krakow, Poland.|Department of Transplantation, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Mordel
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland.|Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pituch-Noworolska
authors.affiliation: Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663, Krakow, Poland. misiedla@cyf-kr.edu.pl.|Department of Clinical Immunology, University Children's Hospital, Wielicka 265, Krakow, Poland. misiedla@cyf-kr.edu.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Siedlar
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009035:Mothers; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011044:Poland; D017422:Sequence Analysis, DNA; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064658:RAG-1 protein
keywords: Omenn syndrome; RAG1/2 genes; Severe combined immunodeficiency