| H00094 | |
| H番号 | H00094 |
| 名称 | DNA修復障害に伴う免疫不全症 |
| 概要 | 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. |
| カテゴリ | 原発性免疫不全症 |
| ネットワーク | nt06504(H00094) Base excision repair nt06506 Double-strand break repair nt06509(H00094) DNA replication |
| 病因遺伝子 | 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] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | - |
| コメント | - |
| リンク | ICD-11: 4A01.31 ICD-10: D82.8 G11.3 MeSH: D001260 D049932 C564694 D001816 OMIM: 208900 604391 251260 210900 606593 609981 617241 |
| 文献 | PMID:12427531 著者 Thompson LH, Schild D タイトル Recombinational DNA repair and human disease. 雑誌 Mutat Res 509:49-78 (2002) DOI:10.1016/S0027-5107(02)00224-5 PMID:17162365 著者 Kumar A, Teuber SS, Gershwin ME. タイトル Current perspectives on primary immunodeficiency diseases. 雑誌 Clin Dev Immunol 13:223-59 (2006) DOI:10.1080/17402520600800705 PMID:9737224 著者 Ten RM. タイトル Primary immunodeficiencies. 雑誌 Mayo Clin Proc 73:865-72 (1998) DOI:10.4065/73.9.865 PMID:15096561 著者 Lim MS, Elenitoba-Johnson KS. タイトル The molecular pathology of primary immunodeficiencies. 雑誌 J Mol Diagn 6:59-83 (2004) DOI:10.1016/S1525-1578(10)60493-X PMID:18424339 著者 Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT. タイトル Genetic diagnosis of primary immune deficiencies. 雑誌 Immunol Allergy Clin North Am 28:387-412, x (2008) DOI:10.1016/j.iac.2008.01.004 PMID:17952897 著者 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. タイトル Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. 雑誌 J Allergy Clin Immunol 120:776-94 (2007) DOI:10.1016/j.jaci.2007.08.053 PMID:22499342 著者 Casey JP, Nobbs M, McGettigan P, Lynch S, Ennis S タイトル Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair. 雑誌 J Med Genet 49:242-5 (2012) DOI:10.1136/jmedgenet-2012-100803 PMID:27427983 (LICS) 著者 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 タイトル Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease. 雑誌 J Clin Invest 126:2881-92 (2016) DOI:10.1172/JCI82890 |