title: NEIL1 is a candidate gene associated with common variable immunodeficiency in a patient with a chromosome 15q24 deletion.
abstract: We report the first patient with an interstitial deletion of chromosome 15q24.1-q24.3 associated with common variable immunodeficiency (CVID). The 18-year old female patient's clinical and immunological phenotype was compared with 8 additional previously published patients with chr15q24 deletions. A CGH analysis estimated the deletion to be 3.767Mb in size (chr15: 74,410,916-78,178,418) and the result was confirmed using qRT-PCR. We defined an immune-related commonly deleted region (ICDR) within the chromosomal band 15q24.2, deleted in all four patients with different forms of antibody deficiencies. Mutations in the 14 genes within this ICDR were not identified in the remaining allele in our patient by WES and gene expression analyses showed haploinsufficiency of all the genes. Among these genes, we consider Nei Like DNA Glycosylase 1 (NEIL1) as a likely candidate gene due to its crucial role in B-cell activation and terminal differentiation.
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Rosa
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Life Sciences, School of Sciences, 1516 Nicosia, Cyprus.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zaravinos
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Liadaki
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Rozina
authors.initials: R
authors.lastname: Caridha
authors.affiliation: Department of Clinical Genetics, Karolinska Institutet Hospital, 17176 Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lundin
authors.affiliation: Department of Women's and Children's Health (KBH), Karolinska University Hospital Solna, 17176 Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Carlsson
authors.affiliation: Division of Pediatrics (CLINTEC), Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Jacek
authors.initials: J
authors.lastname: Winiarski
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarström
authors.affiliation: Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden. Electronic address: lennart.hammarstrom@ki.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics
chemical_list: D045647:DNA Glycosylases; C473634:NEIL1 protein, human
keywords: CVID; DNA repair; Exome sequencing; Immunodeficiency; chr15q24 deletion