INF2 p.Arg214Cys mutation in a Chinese family with rapidly progressive renal failure and follow-up of renal transplantation: case report and literature review

Abstract

Background Heterozygous mutations in the inverted formin 2 (INF2) gene are related to secondary focal segmental glomerulosclerosis (FSGS), a rare secondary disease associated with rapidly progressive renal failure. Case presentation We report a patient with familial autosomal INF2 mutation manifesting nephritic syndromes and elevated serum creatinine levels. Mutational analysis revealed an autosomal dominant (AD) inheritance pattern and a mutation in exon 4 (p.Arg214Cys) of INF2 as the likely cause, which has not been previously described in an Asian family. The patient progressed to end-stage renal disease (ESRD) and received hemodialysis. His mother had undergone renal transplant 3 years earlier, and his grandmother had carried the p.Arg214Cys mutation for more than 80 years without any sign of renal dysfunction. Conclusions This is the first report to identify an association between a familial autosomal dominant INF2 p.Arg214Cys mutation and rapidly progressive renal disease in an Asian family. INF2 mutation analysis should not be restricted to individuals without family history of FSGS, rather it should also be performed on individuals for whom drug-based therapies are not effective. In this case, kidney transplant is an effective alternative.

INF2 and ROBO2 gene mutation in an Indian family with end stage renal failure and follow‐up of renal transplantation

“…(human Inverted formin-2) mutations has been shown in previous reports on western population and Chinese population to having a major role in development of autosomal dominant Focal Segmental Glomerulosclerosis (FSGS), [2][3][4][5] which are histological lesions associated with glomerular degeneration, often progressing to end-stage renal disease (ESRD). 6,7 In few rare cases, INF2 mutations has been correlated with FSGS concurrent to Charot-Marie-Tooth disease, a peripheral nerve affecting degenerative neurological disorder. [7][8][9][10][11] INF2 also plays an important role in maintaining the plasticity of podocytes.…”

“…Formins are conserved group of proteins that regulate the remodelling of actin cytoskeleton during cell polarization, cytokinesis and tissue morphogenesis 1 . INF2 (human Inverted formin‐2) mutations has been shown in previous reports on western population and Chinese population to having a major role in development of autosomal dominant Focal Segmental Glomerulosclerosis (FSGS), 2–5 which are histological lesions associated with glomerular degeneration, often progressing to end‐stage renal disease (ESRD) 6,7 . In few rare cases, INF2 mutations has been correlated with FSGS concurrent to Charot‐Marie‐Tooth disease, a peripheral nerve affecting degenerative neurological disorder 7–11 .…”