title: Novel X-linked syndrome of cardiac valvulopathy, keloid scarring, and reduced joint mobility due to filamin A substitution G1576R.
abstract: Filamin A (FLNA) is known to be involved in intracellular actin binding, cell migration, scaffolding, and signaling. We report a novel X-linked syndrome characterized by cardiac valvular disease, keloid scarring and reduced joint mobility in male second cousins due to a previously unreported mutation in FLNA. Whole exome sequencing was performed using standard methods and segregation analysis was performed in affected and non-affected family members. A novel hemizygous c.4726G>A (p.G1576R) mutation in FLNA was detected. Segregation analysis performed on multiple maternal family members showed c.4726G>A (p.G1576R) segregated with disease in an X-linked inheritance pattern. The findings in these cases are distinct from previously described FLNA related disorders by virtue of decreased joint mobility and spontaneous keloid scarring. They occur in association with a novel mutation and represent a novel genetic syndrome.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California.|Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas.|Mayo Clinic, Center for Individualized Medicine FL, Clinical Genomics, Jacksonville, Florida.
authors.forename: Paldeep Singh
authors.initials: PS
authors.lastname: Atwal
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California.
authors.forename: Sophie
authors.initials: S
authors.lastname: Blease
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Alicia
authors.initials: A
authors.lastname: Braxton
authors.affiliation: Private Practice Oakland, Oakland, California.
authors.forename: Julia
authors.initials: J
authors.lastname: Graves
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Weimin
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Richard
authors.initials: R
authors.lastname: Person
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California.
authors.forename: Leah
authors.initials: L
authors.lastname: Slattery
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California.
authors.forename: Jonathan Adam
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Stanford University, Stanford, California.
authors.forename: Louanne
authors.initials: L
authors.lastname: Hudgins
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D003062:Codon; D019066:Facies; D064448:Filamins / Q000235:genetics*; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007627:Keloid / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D055815:Young Adult
chemical_list: D003062:Codon; D064448:Filamins
keywords: FLNA; G1576R; cardiac valvulopathy; joint hypomobility; keloid scar