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标题：Progeroid laminopathy with restrictive dermopathy-like features caused by an isodisomic LMNA mutation p.R435C
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作者：Sven Starke ; Peter Meinke ; Daria Camozzi 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：6
页码：445-459
出版社：U.S.Department of Health & Human Service
摘要：The. clinical. course. of. a.female.patient.affected. by. a. progeroid.syndrome. with. Restrictive. Dermopathy. (RD)©\likefeatures.was. followed. up..Besides. missing. hairiness,.stagnating.weight. and.growth,. RD©\like. features. including.progressiveskin. swelling. and. solidification,. acrocontractures,. osteolysis. and. muscular. hypotension. were. observed. until. the. patientdied. at. the. age. of. 11. months.. A. homozygous. LMNA. mutation. c.1303C>T. (p.R435C). was. found. by. Sanger. sequencing.Haplotyping. revealed. a. partial. uniparental. disomy. of. chromosome. 1. (1q21.3. to. 1q23.1). including. the. LMNA. gene.. Incontrast. to. reported. RD. patients. with. LMNA. mutations,. LMNA. p.R435C. is. not. located. at. the. cleavage. site. necessary. forprocessing. of. prelamin. A. by. ZMPSTE24. and. leads. to. a. distinct. phenotype. combining. clinical. features. of. RestrictiveDermopathy,. Mandibuloacral. Dysplasia. and. Hutchinson©\Gilford. Progeria.. Functionally,. LMNA. p.R435C. is. associated. withincreasing. DNA. double. strand. breaks. and..decreased. recruitment. of. P53. binding. protein. 1. (53BP1). to. DNA©\damage. sitesindicating. delayed. DNA. repair.. The. follow©\up. of. the. complete. clinical. course. in. the. patient. combined. with. functionalstudies. showed. for. the. first. time. that. a. progressive. loss. of. lamin. A. rather. than. abnormal. accumulation. of. prelamin. Aspecies. could. be. a. pathophysiological. mechanism. in. progeroid. laminopathies,. which. leads. to. DNA. repair. deficiencyaccompanied.by.advancing.tissue.degeneration
关键词：Progeroid.syndrome;.LMNA;.DNA.damage;.uniparental.disomy;.53BP1