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First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation
Author(s) -
Motegi Seiichiro,
Yokoyama Yoko,
Uchiyama Akihiko,
Ogino Sachiko,
Takeuchi Yuko,
Yamada Kazuya,
Hattori Tomoyasu,
Hashizume Hiroaki,
Ishikawa Yuichi,
Goto Makoto,
Ishikawa Osamu
Publication year - 2014
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.12657
Subject(s) - lmna , lamin , progeria , werner syndrome , premature aging , biology , short stature , genetics , cockayne syndrome , pathology , medicine , endocrinology , gene , helicase , rna , nucleotide excision repair , dna repair
Atypical progeroid syndrome ( APS ), including atypical W erner syndrome ( AWS ), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C . We report the first J apanese case of APS / AWS with a LMNA mutation (p.D300N). A 53‐year‐old J apanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS / AWS patient had overlapping features with W erner syndrome ( WS ), such as high‐pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS , including short stature, premature graying/alopecia, cataract, bird‐like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS / AWS .