title: Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie-Tooth neuropathy.
abstract: BACKGROUND
  Mutations in inverted formin, FH2, and WH2 domain containing (INF2) are common causes of dominant focal segmental glomerulosclerosis. INF2 encodes a member of the diaphanous-related formin family, which regulates actin and microtubule cytoskeletons. Charcot-Marie-Tooth neuropathy (CMT) is a group of inherited disorders affecting peripheral neurons. Many reports have shown that glomerulopathy can associate with CMT. However, it has been unclear whether these two processes in the same individual represent one disorder or if they are two separate diseases.
  
  
  METHODS
  Recently, INF2 mutations were identified in 12 of 16 patients with CMT-associated glomerulopathy, suggesting that these mutations are a common cause of the dual phenotype. In this study, we report two cases of CMT-associated glomerulopathy that both showed INF2 mutations. A novel INF2 mutation, p. L77P, was identified in a family in which the dual phenotype was inherited in a dominant fashion. The pathogenic effect of p. L77P was proposed using a structural homology model. In addition, we identified a patient with a sporadic CMT-associated glomerulopathy carrying a known INF2 mutation: p. L128P.
  
  
  CONCLUSIONS
  Our study confirms the link between INF2 mutations and CMT-associated glomerulopathy and widens the spectrum of pathogenic mutations.
authors.affiliation: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Patricia Q
authors.initials: PQ
authors.lastname: Rodriguez
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lohkamp
authors.forename: Gianni
authors.initials: G
authors.lastname: Celsi
authors.forename: Christoph Johannes
authors.initials: CJ
authors.lastname: Mache
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Annika
authors.initials: A
authors.lastname: Wernerson
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D000080865:Formins; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D055815:Young Adult
chemical_list: D000080865:Formins; C546959:INF2 protein, human; D008840:Microfilament Proteins