Immunodeficiency associated with DNA repair defects

Ataxia telangiectasia (AT) [DS:H00064]
Ataxia-telangiectasia-like syndrome [DS:H02014]
Nijmegen 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]

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.

Primary immunodeficiency

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]

PMID:12427531

Thompson LH, Schild D

Recombinational DNA repair and human disease.

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

PMID:17162365

Kumar A, Teuber SS, Gershwin ME.

Current perspectives on primary immunodeficiency diseases.

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

PMID:9737224

Ten RM.

Primary immunodeficiencies.

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

PMID:15096561

Lim MS, Elenitoba-Johnson KS.

The molecular pathology of primary immunodeficiencies.

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

PMID:18424339

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

Genetic diagnosis of primary immune deficiencies.

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

PMID:17952897

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.

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

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

PMID:22499342

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

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

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