Genética hereditária: pesquisas atuais

Abstrato

α-Actinin-4 Gene Mutations, Steroid Responsiveness and FSGS in Adult Onset-Nephrotic Syndrome

Asra Tabassum Fatima Jaffer, Sree Bhushan Raju and Parveen Jahan

Focal segmental glomerulosclerosis (FSGS) is a common pattern of injury seen in primary as well as secondary renal disorders and is a major cause of steroid- resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). SRNS is defined by resistance to standard steroid therapy and it remains one of the most intractable causes of kidney failure. Mutations in α-actinin-4 gene (ACTN4) represent a frequent cause of SRNS associated with an adult onset form of FSGS. We screened a cohort of 374 subjects from the South Indian population for the presence of two missense mutations, K255E and S262P in exon 8 of ACTN4 gene encoding α-actinin-4, an actinfilament crosslinking and bundling protein. Our results revealed that these two mutations were seen only among the patients (4%) in heterozygous form and absent in the controls suggesting that, these mutations were found to be disease causing in nature and the regulation of the actin cytoskeleton of glomerular podocytes may be altered in the patients. Further categorization revealed that K255E and S262P mutations were together responsible for 5% of SRNS and 15% of FSGS cases in our study group. Conversely, these mutations were not found in the controls as well as in the patients with steroid–sensitive nephrotic syndrome (SSNS). This is the first report from India, more studies are warranted to establish the frequency of ACTN4 mutations in our population and such analysis may help in developing mutation(s) specific therapeutic interventions in future.