title: Consanguinity and polygenic diseases: a model for antibody deficiencies.
abstract: Primary immunodeficiencies represent a heterogeneous group of disorders of the immune system, predisposing to various types of infections. Among them, common variable immunodeficiency is the most common symptomatic antibody deficiency. It includes several different forms characterized by defects in the terminal stage of B lymphocyte differentiation, leading to markedly reduced immunoglobulin serum levels and increased susceptibility to bacterial infections. The clinical phenotype is complex, including autoimmunity, granulomatous inflammation, lymphoproliferative disorders and malignancies. Rare autosomal recessive mutations in a number of single genes have recently been reported. However, the underlying genetic defects remain unknown in the majority of cases. In order to seek new genes responsible for the disease, we studied a consanguineous Italian family through exome sequencing combined with homozygosity mapping. Six missense homozygous variants passed our filtering selection and at least two of them were associated with some aspects of the pathological phenotype. Our data remark the complexity of immune system disorders and emphasize the difficulty to understand the significance of genetic results and their correlation with the disease phenotype.
authors: Medical Genetics Unit, S.Orsola-Malpighi University Hospital, Bologna, Italy.
authors: Valentina
authors: V
authors: Di Pierro
authors: Roberta
authors: R
authors: Zuntini
authors: Caterina
authors: C
authors: Cancrini
authors: Andrea
authors: A
authors: Finocchi
authors: Giulia
authors: G
authors: Angelino
authors: Paolo
authors: P
authors: Rossi
authors: Simona
authors: S
authors: Ferrari
mesh_terms: D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000473:pathology*; D003241:Consanguinity; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007558:Italy; D020412:Multifactorial Inheritance / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D017422:Sequence Analysis, DNA