Ataxia-telangiectasia-like syndrome

Immunodeficiency associated with DNA repair defects [DS:H00094]

Ataxia-telangiectasia-like disorder (ATLD) is a very rare autosomal recessive disorder, caused by mutations in Mre11 gene. Mre11 is a member of the Mre11/Rad50/Nbs1 (MRN) protein complex, that acts as a double-strand break sensor and recruits ATM to broken DNA molecules. The clinical features include the progressive cerebellar ataxia, and they are very similar to those of Ataxia-telangiectasia (A-T). In contrast to A-T, ATLD patients don't show telangiectasia and immune deficiency. Recently, genetic heterogeneity of ATLD, caused by mutation in the PCNA gene, has been reported.

Neurodegenerative disease

(ATLD1) MRE11A [HSA:4361] [KO:K10865]
(ATLD2) PCNA [HSA:5111] [KO:K04802]

PMID:15279810

Taylor AM, Groom A, Byrd PJ

Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis.

DNA Repair (Amst) 3:1219-25 (2004)
DOI:10.1016/j.dnarep.2004.04.009

PMID:10612394

Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, Raams A, Byrd PJ, Petrini JH, Taylor AM

The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.

Cell 99:577-87 (1999)
DOI:10.1016/S0092-8674(00)81547-0

PMID:15269180

Delia D, Piane M, Buscemi G, Savio C, Palmeri S, Lulli P, Carlessi L, Fontanella E, Chessa L

MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder.

Hum Mol Genet 13:2155-63 (2004)
DOI:10.1093/hmg/ddh221

PMID:24911150

Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM, Crosby AH

Hypomorphic PCNA mutation underlies a human DNA repair disorder.

J Clin Invest 124:3137-46 (2014)
DOI:10.1172/JCI74593