KEGG DISEASE: Immunodeficiency associated with DNA repair defects

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]
Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS)

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 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
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06509  DNA replication
   H00094  Immunodeficiency associated with DNA repair defects
  nt06504  Base excision repair
   H00094  Immunodeficiency associated with DNA repair defects
  nt06506  Double-strand break repair
   H00094  Immunodeficiency associated with DNA repair defects

Pathway

hsa03440

Homologous recombination

hsa03450

Non-homologous end-joining

hsa03410

Base excision repair

Network

nt06504 Base excision repair
nt06506 Double-strand break repair
nt06509 DNA replication

Gene

ATM [HSA:472] [KO:K04728]
MRE11A [HSA:4361] [KO:K10865]
NBS1(Nibrin) [HSA:4683] [KO:K10867]
LIG1 [HSA:3978] [KO:K10747]
LIG4 [HSA:3981] [KO:K10777]
BLM [HSA:641] [KO:K10901]
MCM4 [HSA:4173] [KO:K02212]
(LICS) NSMCE3 [HSA:56160] [KO:K22823]

Other DBs

ICD-11:

4A01.31

MeSH:

D001260 D049932 C564694 D001816

OMIM:

208900 604391 251260 210900 606593 609981 617241

Reference

PMID:12427531

Authors

Thompson LH, Schild D

Title

Recombinational DNA repair and human disease.

Journal

Mutat Res 509:49-78 (2002)
DOI:10.1016/S0027-5107(02)00224-5

Reference

PMID:17162365

Authors

Kumar A, Teuber SS, Gershwin ME.

Title

Current perspectives on primary immunodeficiency diseases.

Journal

Clin Dev Immunol 13:223-59 (2006)
DOI:10.1080/17402520600800705

Reference

PMID:9737224

Authors

Ten RM.

Title

Primary immunodeficiencies.

Journal

Mayo Clin Proc 73:865-72 (1998)
DOI:10.4065/73.9.865

Reference

PMID:15096561

Authors

Lim MS, Elenitoba-Johnson KS.

Title

The molecular pathology of primary immunodeficiencies.

Journal

J Mol Diagn 6:59-83 (2004)
DOI:10.1016/S1525-1578(10)60493-X

Reference

PMID:18424339

Authors

Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.

Title

Genetic diagnosis of primary immune deficiencies.

Journal

Immunol Allergy Clin North Am 28:387-412, x (2008)
DOI:10.1016/j.iac.2008.01.004

Reference

PMID:17952897

Authors

Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.

Title

Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.

Journal

J Allergy Clin Immunol 120:776-94 (2007)
DOI:10.1016/j.jaci.2007.08.053

Reference

PMID:22499342

Authors

Casey JP, Nobbs M, McGettigan P, Lynch S, Ennis S

Title

Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair.

Journal

J Med Genet 49:242-5 (2012)
DOI:10.1136/jmedgenet-2012-100803

Reference

PMID:27427983 (LICS)

Authors

van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, Harakalova M, Chinn IK, Alt A, Vondrova L, Hochstenbach R, van Montfrans JM, Terheggen-Lagro SW, van Lieshout S, van Roosmalen MJ, Renkens I, Duran K, Nijman IJ, Kloosterman WP, Hennekam E, Orange JS, van Hasselt PM, Wheeler DA, Palecek JJ, Lehmann AR, Oliver AW, Pearl LH, Plon SE, Murray JM, van Haaften G

Title

Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease.

Journal

J Clin Invest 126:2881-92 (2016)
DOI:10.1172/JCI82890

LinkDB

» Japanese version

DBGET integrated database retrieval system