INF2 mutations associated with dominant inherited intermediate Charcot-Marie-Tooth neuropathy with focal segmental glomerulosclerosis in two Chinese patients.

Recently, mutations in the inverted formin 2 (INF2) gene have been indentified in patients with dominant inherited intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) with focal segmental glomerulosclerosis (FSGS). We report clinical and nerve pathological changes in two Chinese patients. Case 1 is 27 years old and presented with distal muscle weakness and atrophy of legs at the age of 13 and renal failure at the age of 26. Three of his family members died due to pure renal failure. Case 2 is 22 years old and presented with distal muscle weakness and atrophy of the legs with transient attacks of difficulty in speaking at age 17. Proteinuria was found by routine urine test at the same time. Sural nerve biopsy revealed moderate-to-severe loss of myelinated fibers with union bulbs and regeneration clusters in both patients. Ultrastructurally, numerous elongated extensions of Schwann cells of unmyelinated fibers could be seen in both patients. INF2 gene mutation screening revealed c.451 T>C in case 1 and c.341 G>A in case 2. This is the first report of Chinese patients with INF2-related DI-CMT. The c.451 T>C mutant was responsible for both isolated FSGS and a dual phenotype of FSGS and neuropathy within one family. Intrafamilial variability can be found with the same INF2 mutation. The CNS manifestations further broadened the clinical spectrum of INF2- associated disorders.