0000000000205785
AUTHOR
Anne Guiochon-mantel
Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenital
BackgroundArthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the genetic diagnosis rates of AMC, to evaluate the added value of whole exome sequencing (WES) compared with targeted exome sequencing (TES) and to identify new genes in 315 unrelated undiagnosed AMC families.MethodsSeveral genomic approaches were used including genetic mapping of disease loci in multiplex or consanguineous families, TES then WES. Sanger sequencing was performed to identify or validate variants.ResultsWe achieved disease gene identification in 52.7% of AMC index pati…
High level of plasma estradiol as a new predictor of ischemic arterial disease in older postmenopausal women: the three-city cohort study.
Background Despite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain. Methods and Results In the Three‐City prospective cohort study of subjects (n=9294) >65 years of age, we investigated the association of total 17β‐estradiol, bioavailable 17β‐estradiol, and total testosterone with the 4‐year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case–cohort study including a random sample of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional‐hazards model…