Consanguinity and polygenic diseases: A model for antibody deficiencies

Valentina Di Pierro, Roberta Zuntini, Caterina Cancrini, Andrea Finocchi, Giulia Angelino, Paolo Rossi, Simona Ferrari

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalHuman Heredity
Volume77
Issue number1-4
DOIs
Publication statusPublished - 2014

Fingerprint

Consanguinity
Phenotype
Antibodies
Immune System
Common Variable Immunodeficiency
Exome
Lymphoproliferative Disorders
Immune System Diseases
Autoimmunity
Bacterial Infections
Genes
Immunoglobulins
B-Lymphocytes
Inflammation
Mutation
Infection
Serum
Neoplasms

Keywords

  • Antibody deficiencies
  • Common variable immunodeficiency
  • Consanguinity

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Consanguinity and polygenic diseases : A model for antibody deficiencies. / Di Pierro, Valentina; Zuntini, Roberta; Cancrini, Caterina; Finocchi, Andrea; Angelino, Giulia; Rossi, Paolo; Ferrari, Simona.

In: Human Heredity, Vol. 77, No. 1-4, 2014, p. 144-149.

Research output: Contribution to journalArticle

Di Pierro, Valentina ; Zuntini, Roberta ; Cancrini, Caterina ; Finocchi, Andrea ; Angelino, Giulia ; Rossi, Paolo ; Ferrari, Simona. / Consanguinity and polygenic diseases : A model for antibody deficiencies. In: Human Heredity. 2014 ; Vol. 77, No. 1-4. pp. 144-149.
@article{49fd0a9a9da443c3a6cee342fb0a9a6a,
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.",
keywords = "Antibody deficiencies, Common variable immunodeficiency, Consanguinity",
author = "{Di Pierro}, Valentina and Roberta Zuntini and Caterina Cancrini and Andrea Finocchi and Giulia Angelino and Paolo Rossi and Simona Ferrari",
year = "2014",
doi = "10.1159/000362364",
language = "English",
volume = "77",
pages = "144--149",
journal = "Human Heredity",
issn = "0001-5652",
publisher = "S. Karger AG",
number = "1-4",

}

TY - JOUR

T1 - Consanguinity and polygenic diseases

T2 - A model for antibody deficiencies

AU - Di Pierro, Valentina

AU - Zuntini, Roberta

AU - Cancrini, Caterina

AU - Finocchi, Andrea

AU - Angelino, Giulia

AU - Rossi, Paolo

AU - Ferrari, Simona

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Antibody deficiencies

KW - Common variable immunodeficiency

KW - Consanguinity

UR - http://www.scopus.com/inward/record.url?scp=84904860313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904860313&partnerID=8YFLogxK

U2 - 10.1159/000362364

DO - 10.1159/000362364

M3 - Article

C2 - 25060277

AN - SCOPUS:84904860313

VL - 77

SP - 144

EP - 149

JO - Human Heredity

JF - Human Heredity

SN - 0001-5652

IS - 1-4

ER -