INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.

BACKGROUND: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. METHODS: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. RESULTS: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. CONCLUSIONS: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).

[Renal graft rupture]. / Traitement conservateur d'une rupture du greffon rénal.

Spontaneous rupture of the renal graft is a serious early complication of renal transplantation, which can be responsible for loss of the graft. It usually follows an episode of acute rejection or acute tubular necrosis. It has a poor prognosis, as treatment consists of graft nephrectomy in the majority of cases. The authors report a case of renal graft rupture discovered during reoperation for severe bleeding. Rupture was secondary to acute tubular necrosis. Treatment is designed to preserve the kidney. The outcome was favourable with complete recovery of graft function.

[Effects of anxiety and depression on haemodialysis adequacy]. / Troubles anxio-dépressifs et qualité de l'hémodialyse.

UNLABELLED: Depression and anxiety are the most commonly encountered psychological problems in patients with end-stage renal disease, especially those on renal replacement therapy. We sought to assess the prevalence of anxiety and depressive symptoms in patients undergoing haemodialysis treatment and to establish the relationship between these psychological problems and criteria of haemodialysis adequacy. METHODS: We implemented a transversal study on 93 adult haemodialysis patients recruited from in Ibn-Sina Haemodialysis department in Rabat in April 2003. They underwent three tests performed by a psychiatrist. The first one was the brief psychiatric rating scale (BPRS) and then Hamilton anxiety and depression rating scales. We also studied anthropometric features, comorbidity, dialysis session's characteristics, and the following haemodialysis adequacy parameters: extracellular volume, nitrogenous retention, nutritional status, phosphocalcic balance, serum potassium, acid-basic equilibrium, anaemia, and inflammatory markers. RESULTS: The mean (+/-SD) age of our population was 42+/-15.5. The sex-ratio was 1.11 (49 W/44 M). Only one patient had a history of psychological care by a psychiatrist. The prevalence of depression and anxiety among the patients surveyed was 67 and 69.3% respectively. Seven patients had a severe depression. We did not found any other psychological condition by BPRS. Depression has been shown to be associated to several haemodialysis adequacy markers like high blood pressure, interdialytic weight intake, nutritional parameters (serum albumin concentration...), and serum creatinin concentration. Depression was more frequent in women, diabetics, and patients with C hepatitis. CONCLUSION: This study will be continued by a prospective screening of patients under appropriate therapy.