title: A novel mutation, outside of the candidate region for diagnosis, in the inverted formin 2 gene can cause focal segmental glomerulosclerosis.
abstract: Focal and segmental glomerulosclerosis (FSGS) is a histological pattern that has several etiologies, including genetics. The autosomal dominant form of FSGS is a heterogenic disease caused by mutations within three known genes: α-actinin 4 (ACTN4), canonical transient receptor potential 6 (TRPC6), and the inverted formin 2 (INF2) gene. More recently, INF2 mutations have also been attributed to Charcot-Marie-Tooth neuropathy associated with FSGS. Here we performed direct sequencing, histological characterization, and functional studies in a cohort of families with autosomal dominant FSGS. We detected a novel mutation in exon 6 of the INF2 gene outside of the exon 2-4 candidate region used for rapid diagnosis of autosomal dominant FSGS. This new mutation is predicted to alter a highly conserved amino-acid residue within the 17th α-helix of the diaphanous inhibitory domain of the protein. A long-term follow-up of this family indicated that all patients were diagnosed in adulthood, as opposed to early childhood, and progression to end-stage renal disease was at different times without clinical or electrodiagnostic evidence of neuropathy. Thus, this novel mutation in INF2 linked to nonsyndromic FSGS indicates the necessity for full gene sequencing if no mutation is found in the current rapid-screen region of the gene.
authors.affiliation: Laboratory of Nephrology, Sanitary Research Institute (IDIS), Santiago de Compostela, Spain. maria.sanchez.ares@gmail.com
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Ares
authors.forename: Marina
authors.initials: M
authors.lastname: Garcia-Vidal
authors.forename: Espinosa-Estevez
authors.initials: EE
authors.lastname: Antucho
authors.forename: Pardo
authors.initials: P
authors.lastname: Julio
authors.forename: Vazquez-Martul
authors.initials: VM
authors.lastname: Eduardo
authors.forename: Xose M
authors.initials: XM
authors.lastname: Lens
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Garcia-Gonzalez
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D013030:Spain / Q000453:epidemiology
chemical_list: D009419:Nerve Tissue Proteins