Kyla A Britson1,2, Stephanie Y Yang1,3, Thomas E Lloyd4. 1. Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Graduate program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Graduate program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. tlloyd4@jhmi.edu.
Abstract
PURPOSE OF REVIEW: Our goal is to review the recent literature pertaining to the genetics of sporadic inclusion body myositis (IBM). RECENT FINDINGS: In a study of 252 IBM patients, the class II MHC allele HLA-DRB1*03:01 showed the most significant association with IBM, and that risk could be largely attributed to amino acids within the peptide-binding pocket. Candidate gene sequencing identified rare missense variants in proteins regulating protein homeostasis including VCP and SQSTM1. An unbiased approach employing exome sequencing of genes encoding rimmed vacuole proteins identified FYCO1 variants in IBM. Ongoing GWAS approaches may shed new light on genetic risk factors for IBM. Many variants have been reported at an increased frequency in IBM in small studies; however, only HLA association has shown genome-wide significance. Future studies are needed to validate variants in larger cohorts and to understand the molecular roles these risk factors play in IBM.
PURPOSE OF REVIEW: Our goal is to review the recent literature pertaining to the genetics of sporadic inclusion body myositis (IBM). RECENT FINDINGS: In a study of 252 IBM patients, the class II MHC allele HLA-DRB1*03:01 showed the most significant association with IBM, and that risk could be largely attributed to amino acids within the peptide-binding pocket. Candidate gene sequencing identified rare missense variants in proteins regulating protein homeostasis including VCP and SQSTM1. An unbiased approach employing exome sequencing of genes encoding rimmed vacuole proteins identified FYCO1 variants in IBM. Ongoing GWAS approaches may shed new light on genetic risk factors for IBM. Many variants have been reported at an increased frequency in IBM in small studies; however, only HLA association has shown genome-wide significance. Future studies are needed to validate variants in larger cohorts and to understand the molecular roles these risk factors play in IBM.
Entities:
Keywords:
FYCO1; Follistatin; HLA; Inclusion body myositis; SQSTM1; VCP
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