Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly

Matsumoto, Yoshiyuki; Miyamoto, Tatsuo; Sanada, Hiromi; Izumi, Hideki; Nakazawa, Yuka; Ogi, Tomoo; Tahara, Hidetoshi; Oku, Shozo; Hiramoto, Azuma; Shiiki, Toshihide; Fujisawa, Yoshiki; Ohashi, Hirofumi; Sakemi, Yoshihiro; Matsuura, Shinya

doi:10.1016/j.dnarep.2010.12.002

Cited by 53 publications

(57 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Presently, the literature describes 18 cases of ATLD and one case of NBSLD that were all linked to mutations in the MRE11 gene and one NBSLD patient with two RAD50 mutations (Hernandez et al 1993;Stewart et al 1999;Pitts et al 2001;Delia et al 2004;Fernet et al 2005;Uchisaka et al 2009;Matsumoto et al 2011;Palmeri et al 2013). The availability of atomic structures of eukaryotic Mre11 and Nbs1 and prokaryotic Rad50 and the high degree of conservation of MRN allow us to map the underlying mutations onto a structural model of the MRN complex (Fig.…”

Section: Mutations In Mre11-rad50-nbs1 In Human Diseasementioning

confidence: 99%

“…All three MRN-associated syndromes and A-T share phenotypes on a cellular level, but patients differ with respect to the extent of neurological, immunological, andcancer predisposition disorders. Whereas NBS and NBSLD lead to microcephaly, A-Tand ATLD are associated with neurodegeneration Varon et al 1998;Stewart et al 1999;Maser et al 2001;Waltes et al 2009;Matsumoto et al 2011).…”

Section: Mutations In Mre11-rad50-nbs1 In Human Diseasementioning

confidence: 99%

See 1 more Smart Citation

Structural Studies of DNA End Detection and Resection in Homologous Recombination

Schiller

Seifert

Linke-Winnebeck

et al. 2014

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

DNA double-strand breaks are repaired by two major pathways, homologous recombination or nonhomologous end joining. The commitment to one or the other pathway proceeds via different steps of resection of the DNA ends, which is controlled and executed by a set of DNA double-strand break sensors, endo-and exonucleases, helicases, and DNA damage response factors. The molecular choreography of the underlying protein machinery is beginning to emerge. In this review, we discuss the early steps of genetic recombination and double-strand break sensing with an emphasis on structural and molecular studies.

show abstract

Section: Mutations In Mre11-rad50-nbs1 In Human Diseasementioning

confidence: 99%

Section: Mutations In Mre11-rad50-nbs1 In Human Diseasementioning

confidence: 99%

Structural Studies of DNA End Detection and Resection in Homologous Recombination

Schiller

Seifert

Linke-Winnebeck

et al. 2014

Cold Spring Harbor Perspectives in Biology

View full text Add to dashboard Cite

show abstract

“…This distinction has been further confused by a recent description of MRE11-deficient patients with features of NBS (i.e. microcephaly) and not progressive ataxia [87].…”

Section: Related Radiosensitive Immunodeficiency Disordersmentioning

confidence: 96%

Reprint of “The clinical impact of deficiency in DNA non-homologous end-joining”

2014

View full text Add to dashboard Cite

Double strand break repair V(D)J recombination (Severe) combined immunodeficiency -(S)CID Human syndromes a b s t r a c t DNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway in mammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models, since radiation potently induces DSBs. The process of V(D)J recombination functions during the development of the immune response, and involves the introduction and rejoining of programmed DSBs to generate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJ deficiency confers (severe) combined immunodeficiency -(S)CID -due to a failure to carry out V(D)J recombination efficiently. NHEJ also functions in class switch recombination, another step enhancing T and B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patients revealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syndromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have been identified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCID patients frequently display additional characteristics including microcephaly, dysmorphic facial features and growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our current understanding of the underlying biology.

show abstract

“…An original report described ATLD as a milder phenotype of AT. However, a more severe phenotype including microcephaly or NBS-like dimorphic features has been reported [25,26]. MRE11A mutation affects M/R/N complex stability, and decreased NBS1 and/or RAD50 is observed.…”

Section: Ataxia Telangiectasia-like Disorder (Atld)mentioning

confidence: 99%

XCIND as a genetic disease of X-irradiation hypersensitivity and cancer susceptibility

Mizutani

Takagi

2012

Int J Hematol

View full text Add to dashboard Cite

The XCIND syndrome is named after distinct hypersensitivity to ionizing (X-ray) irradiation, cancer susceptibility, immunodeficiency, neurological abnormality, and double-strand DNA breakage. The disorders comprising XCIND syndrome are usually inherited in an autosomal recessive manner. Ataxia telangiectasia (A-T) is one such disease, and is caused by biallelic germline mutation of the Ataxia telangiectasia mutated (ATM) gene. Heterozygous carriers of the ATM mutation, who do not show A-T-like clinical symptoms, are estimated to comprise 1 % of the population. Thus, understanding the biological basis of XCIND, including A-T, should help shed light on the pathogenesis of genetic diseases with cancer susceptibility.

show abstract

Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly

Cited by 53 publications

References 24 publications

Structural Studies of DNA End Detection and Resection in Homologous Recombination

Structural Studies of DNA End Detection and Resection in Homologous Recombination

Reprint of “The clinical impact of deficiency in DNA non-homologous end-joining”

XCIND as a genetic disease of X-irradiation hypersensitivity and cancer susceptibility

Contact Info

Product

Resources

About