Journal article
Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis
Kidney international, Vol.83(2), pp.316-322
02/01/2013
DOI: 10.1038/ki.2012.349
PMCID: PMC3647680
PMID: 23014460
Abstract
Mutations in the inverted formin 2 gene (INF2) have recently been identified as the most common cause of autosomal dominant focal and segmental glomerulosclerosis (FSGS). To quantify the contribution of various genes contributing to FSGS, we sequenced INF2 where all mutations have previously been described (exons 2 to 5) in a total of 215 probands and 281 sporadic individuals with FSGS, along with other known genes accounting for autosomal dominant FSGS (ACTN4, TRPC6, and CD2AP) in 213 probands. Variants were classified as disease-causing if they altered the amino acid sequence and if they were not found in control samples and in families segregated with disease. Mutations in INF2 were found in a total of 20 of the 215 families (including those previously reported) in our cohort of autosomal dominant familial nephrotic syndrome or FSGS, thereby explaining disease in 9%. INF2 mutations were found in 2 of 281 individuals with sporadic FSGS. In contrast, ACTN4- and TRPC6-related diseases accounted for 3 and 2% of our familial cohort, respectively. INF2-related disease showed variable penetrance, with onset of disease ranging widely from childhood to adulthood, and commonly leading to end-stage renal disease in the third and fourth decade of life. Thus, mutations in INF2 are a more common, although still a minor, monogenic cause of familial FSGS when compared with other known autosomal dominant genes associated with FSGS. Kidney International (2013) 83, 316-322; doi:10.1038/ki.2012.349; published online 26 September 2012
Details
- Title: Subtitle
- Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis
- Creators
- Moumita Barua - Beth Israel Deaconess Medical CenterElizabeth J. Brown - Beth Israel Deaconess Medical CenterVictoria T. Charoonratana - Beth Israel Deaconess Medical CenterGiulio Genovese - Beth Israel Deaconess Medical CenterHua Sun - Beth Israel Deaconess Medical CenterMartin R. Pollak - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.83(2), pp.316-322
- Publisher
- Springer Nature
- DOI
- 10.1038/ki.2012.349
- PMID
- 23014460
- PMCID
- PMC3647680
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Number of pages
- 7
- Grant note
- NephCure foundation HL-102924 / WHI Sequencing Project HL-102926 / Seattle GO Sequencing Project RC2HL102925 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL-102925 / Broad GO Sequencing Project Kidney Research Scientist Core Education and National Training Program K12HD052896 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) DK54931; 5K12HDO52896 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Canadian Society of Nephrology and Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) R56DK054931 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) HL-103010 / Heart GO Sequencing Project HL-102923 / Lung GO Sequencing Project
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics
- Record Identifier
- 9984384757402771
Metrics
5 Record Views