Screening of ACTN4 and TRPC6 mutations in a Chinese cohort of patients with adult-onset familial focal segmental glomerulosclerosis.

OBJECTIVES: Familial focal segmental glomerulosclerosis (FSGS) has been widely reported as having an underlining genetic component to its pathogenesis. Recently, mutations in TRPC6 and ACTN4 were identified to be associated with familial FSGS, however few studies have reported the mutation rates of these two genes in Chinese familial FSGS patients. The aim of this study was to determine the prevalence of TRPC6 and ACTN4 mutations in Chinese adult-onset familial FSGS.

METHODS: 80 FSGS pedigrees with Chinese ancestry who were admitted to our hospital from September 1997 to January 2012 were screened for TRPC6 and ACTN4 mutations. There was at least one biopsy-proven FSGS in each family. An additional family member with renal function insufficiency, obvious proteinuria, or end-stage renal disease was required if there was only 1 biopsy-proven FSGS case in the family. FSGS secondary to systemic diseases, such as obesity, hypertension, diabetes, or virus infection, were excluded. Other hereditary renal diseases, such as Alport's disease and Fabry disease, were also excluded by related tests. Genomic DNA was extracted from peripheral blood cells, and Sanger sequencing was performed for all exons and exon-intron boundaries of TRPC6 and ACTN4 in the probands of all FSGS pedigrees enrolled in this study.

RESULTS: Of the total index patients, 33 were female and 47 were male. The median age at disease onset was 39 years (range 15-67). The median proteinuria level was 1,324 mg/day and the median serum creatinine level was 114.5 μmol/l (range 41-1,040) at diagnosis. A missense mutation (Q889K) of TRPC6 was found in two independent families. No mutation was found in ACTN4. Accordingly, the mutation rate of TRPC6 was 2.5% and of ACTN4 it was 0%.

CONCLUSION: Mutations of TRPC6 and ACTN4 occur in only a minor portion of Chinese familial FSGS patients. Further genetic studies conducted in these patients will be helpful to increase our understanding of the pathogenesis of FSGS.