title: A case of Werner syndrome without metabolic abnormality: implications for the early pathophysiology.
abstract: Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN DNA helicase. It is characterized by the graying and loss of hair, juvenile cataracts, sclerosis and ulceration of skin, insulin-resistant diabetes mellitus, dyslipidemia, abdominal adiposity, osteoporosis, atherosclerosis, and malignant neoplasm. Patients are usually diagnosed in their 30s or 40s, but the early pathophysiology of the syndrome is still not fully understood. Here we report a 29-year-old female patient who displayed cataracts, hair graying, and tendinous calcinosis. Her parents were first cousins. Interestingly, the patient lacked the metabolic signs typical for WS, including glucose intolerance, dyslipidemia, and visceral fat accumulation. A hyperinsulinemic response at 30 min was observed in an oral glucose tolerance test. Mutational analysis for the WRN gene revealed a homozygous nucleotide substitution 3190C>T in exon 24, resulting in a protein product with replacement of an arginine residue at position 573 by termination codon (Arg987Ter). The mutated WRN protein was unable to translocate into the nucleus in an in vitro cell assay. A WS patient with an Arg987Ter mutation has been previously reported in Switzerland, the present case is the first to be identified in Asia. This case demonstrates the early clinical features of WS and suggests that metabolic abnormality, including insulin resistance, is not an essential component of WS at disease onset. Moreover, a follow-up study of such case would be useful to understand how the various clinical symptoms in WS develop and progress over the years.
authors.affiliation: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Takada-Watanabe
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.forename: Minoru
authors.initials: M
authors.lastname: Takemoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Irisuna
authors.forename: Satoshi
authors.initials: S
authors.lastname: Honjo
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Futami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase