title: Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.
abstract: BACKGROUND
  Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet.
  
  
  METHODS
  We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein.
  
  
  RESULTS
  Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT.
  
  
  CONCLUSIONS
  We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.
authors.affiliation: Laboratory on Pathophysiology of Uremia and Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.affiliation: Laboratory on Pathophysiology of Uremia and Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lugani
authors.affiliation: Laboratory on Pathophysiology of Uremia and Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Dagnino
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Gigante
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University Federico II of Naples - CEINGE - Advanced Biotechnologies, Napoli, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University Federico II of Naples - CEINGE - Advanced Biotechnologies, Napoli, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Falco
authors.affiliation: Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.affiliation: Nephrology, Dialysis, Transplantation Unit, Azienda Ospedaliera-University of Padova, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.affiliation: Nefrologia, Dialisi, Trapianti Renali, O.C. Ca' Foncello, ULSS 9, Treviso, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Department of Medicine, Nephrology Unit, University of Padoa, Padova, Italy.
authors.forename: Dorella
authors.initials: D
authors.lastname: Del Prete
authors.affiliation: Nephrology and Dialysis Unit, 'San Giovanni di Dio' Hospital, Agrigento, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Granata
authors.affiliation: Nephrology and Dialysis Unit, Ospedale Alta Val D'Elsa, Poggibonsi, Siena, Italy.
authors.forename: Donella
authors.initials: D
authors.lastname: Borracelli
authors.affiliation: Nephrology and Dialysis Unit, Ospedale S. Croce e Carle, Cuneo, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moggia
authors.affiliation: Nephrology and Transplantation Unit, Department of Translational Medicine, Azienda Ospedaliero-Universitaria 'Maggiore della Carità', 'Amedeo Avogadro' University, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.affiliation: Neurology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rinaldi
authors.affiliation: Renal, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.affiliation: Laboratory on Pathophysiology of Uremia and Division of Nephrology, Dialysis, Transplantation, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D000080865:Formins; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D007558:Italy; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
chemical_list: D017931:DNA Primers; D000080865:Formins; C546959:INF2 protein, human; D008840:Microfilament Proteins
keywords: INF2 gene; focal segmental glomerulosclerosis; mutation analysis; proteinuria