Lauren Kerr, Pierre Moffatt, Lauren Hyer, Sarah Nossov, Noémi Dahan-Oliel, Frank Rauch
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引用次数: 0
Abstract
Arthrogryposis multiplex congenita (AMC) is a group of conditions with congenital joint contractures in at least two body regions. ACTC1 variants cause heart disorders but have also been reported in six families with AMC. We report on two individuals with AMC who were heterozygous for ACTC1 missense variants (NM_005159.5; c.325G>A, p.Glu109Lys and c.650A>C, p.Lys217Thr). Individual 1 had scoliosis and no reported cardiac phenotype. Individual 2 had Shone's complex with coarctation of the aorta, which has not been reported in ACTC1-related AMC before. In vitro testing demonstrated that p.Glu109Lys caused impaired actin filament assembly and reduced ACTC1 protein levels, effects not apparent for p.Lys217Thr. Our findings characterize two novel variants that cause ACTC1-related AMC and expand the list of phenotypes observed in this disorder.
期刊介绍：
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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