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

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 35–40 years 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 α-actinin and α-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.