title: A novel heterozygous deletion-insertion mutation (2695-2712 del/GTTTGT ins) in exon 18 of the filamin C gene causes filaminopathy in a large Chinese family.
abstract: Filaminopathy represents a rare subgroup of myofibrillar myopathies caused by mutation in filamin C gene. We present a Chinese family with filaminopathy, characterized by onset at the age of 35-40years with progressive muscle weakness in all limbs. Mild cardiac symptoms and chronic diarrhea were present in a few patients. Muscle biopsy revealed numerous spheroid bodies and amorphous deposits in the fibers, which were positive for desmin, dysferlin, dystrophin and ubiquitin, but negative for alpha-actinin and alpha-synuclein. Ultrastructural analysis revealed inclusions composed of disorganized thin filaments and interspersed electron-dense granules, accumulating in spheroid or cytoplasmic structures. A novel complex mutation of 18-nucleotide deletion and 6-nucleotide insertion was identified in exon 18 of the filamin C gene, resulting in an in-frame 6 amino acid deletion (Lys899-Val904) and a 2 amino acid insertion (Val 899-Cys900) in the seventh Ig-like repeat of filamin C. Our findings expand the genetic spectrum and geographic distribution of filaminopathy.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Luan
authors.forename: Daojun
authors.initials: D
authors.lastname: Hong
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D003285:Contractile Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D064448:Filamins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008854:Microscopy, Electron; D008875:Middle Aged; D008958:Models, Molecular; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D009210:Myofibrils / Q000473:pathology*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics / Q000502:physiology*
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D009124:Muscle Proteins