DISEASE: Immunodeficiency associated with DNA repair defects
Entry
H00094 Disease
Name
Immunodeficiency associated with DNA repair defects
Subgroup
Ataxia telangiectasia (AT) [DS:H00064] Ataxia-telangiectasia-like syndrome [DS:H02014] Nijmegen breakage syndrome [DS:H01344] DNA ligase I deficiency DNA ligase IV deficiency [DS:H02015] Bloom syndrome [DS:H01346] IMAGE-I syndrome [DS:H02369] FILS syndrome [DS:H02370]
Supergrp
Disorders of adaptive immunity [DS:H02526] Primary immunodeficiency disease [DS:H01725]
Description
A number of genetically determined disorders collectively called as the chromosome breakage syndromes or DNA-repair disorders have a characteristic cytogenetic feature, chromosome instability. They are all autosomal recessive, show an increased tendency for chromosomal aberrations and to develop malignancies. Ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), and an ataxia-like disorder (ATLD), are chromosome instability disorders that are defective in the ataxia telangiectasia mutated (ATM), NBS, and Mre11 genes, respectively. These genes are critical in maintaining cellular resistance to ionizing radiation (IR), which kills largely by the production of double-strand breaks (DSBs). Bloom syndrome involves a defect in the BLM helicase, which seems to play a role in restarting DNA replication forks that are blocked at lesions, thereby promoting chromosome stability. A point mutational change in DNA ligase I was identified in a unique immunodeficient individual who suffered recurrent sinopulmonary infection leading to bronchiectasis. A non-inactivating mutational change in DNA ligase IV has also been identified in a leukaemia patient, who was dramatically over-sensitive to radiotherapy.
Category
Primary immunodeficiency
Brite
Human diseases [BR:br08402]
Immune system diseases
Primary immunodeficiency
H00094 Immunodeficiency associated with DNA repair defects
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Primary immunodeficiencies
4A01 Primary immunodeficiencies due to disorders of adaptive immunity
H00094 Immunodeficiency associated with DNA repair defects
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
