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

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• 作者：Yoshiyuki Matsumoto^a ; Tatsuo Miyamoto^a ; Hiromi Sakamoto^a ; Hideki Izumi^a ; Yuka Nakazawa^b ; Tomoo Ogi^b ; Hidetoshi Tahara^c ; Shozo Oku^d ; Azuma Hiramoto^e ; Toshihide Shiiki^f ; Yoshiki Fujisawa^g ; Hirofumi Ohashi^h ; Yoshihiro Sakemiⁱ ; Shinya Matsuura^a ; ^{shinya@hiroshima-u.ac.jp}
• 关键词：Nijmegen breakage syndrome (NBS) ; Ataxia– ; telangiectasia-like disorder (ATLD) ; Nijmegen breakage syndrome-like disorder (NBSLD) ; ATM ; MRE11 ; NBS1 ; Microcephaly
• 刊名：DNA Repair
• 出版年：2011
• 出版时间：7 March 2011
• 年：2011
• 卷：10
• 期：3
• 页码：314-321
• 全文大小：1019 K

文摘

MRE11 and NBS1 function together as components of a MRE11/RAD50/NBS1 protein complex, however deficiency of either protein does not result in the same clinical features. Mutations in the NBN gene underlie Nijmegen breakage syndrome (NBS), a chromosomal instability syndrome characterized by microcephaly, bird-like faces, growth and mental retardation, and cellular radiosensitivity. Additionally, mutations in the MRE11A gene are known to lead to an ataxia–telangiectasia-like disorder (ATLD), a late-onset, slowly progressive variant of ataxia–telangiectasia without microcephaly. Here we describe two unrelated patients with NBS-like severe microcephaly (head circumference −10.2 SD and −12.8 SD) and mutations in the MRE11A gene. Both patients were compound heterozygotes for a truncating or missense mutation and carried a translationally silent mutation. The truncating and missense mutations were assumed to be functionally debilitating. The translationally silent mutation common to both patients had an effect on splicing efficiency resulting in reduced but normal MRE11 protein. Their levels of radiation-induced activation of ATM were higher than those in ATLD cells.