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 25 prevalence of the association has not been assessed yet. Methods. We screened 28 families with AD FSGS and identified eight 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. 30 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 ESRD during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 35 are 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. 40 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 been for the first time here calculated to be 12.5% of mutation carriers. Our 45 findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.