FAT1 biallelic truncating mutation causes a non-syndromic proteinuria in a child
- PDF / 1,615,201 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 77 Downloads / 165 Views
CASE REPORT
FAT1 biallelic truncating mutation causes a non‑syndromic proteinuria in a child Rini Rossanti1 · Toshio Watanabe2 · China Nagano1 · Shigeo Hara3 · Tomoko Horinouchi1 · Tomohiko Yamamura1 · Nana Sakakibara1 · Takeshi Ninchoji1 · Kazumoto Iijima1 · Kandai Nozu1 Received: 20 July 2020 / Accepted: 28 August 2020 © Japanese Society of Nephrology 2020
Abstract The identification of monogenic causes in patients with proteinuria has revealed that the encoded proteins functionally participate in distinct cellular tasks and signaling pathways in the slit diaphragms of the glomerular basement membrane. FAT1 is a member of a small family of vertebrate-cadherin-like genes, which is a crucial component in slit diaphragms and has a vital role in tubular regeneration. Only 5 cases with glomerulonephritis having FAT1 gene biallelic variants have been reported. However, only one had the biallelic truncating variant, and others had missense variants. Therefore, we need further evidence of this gene being responsible for steroid-resistant nephrotic syndrome (SRNS) or glomerulonephritis. Here we describe a 5-year-old boy in who proteinuria was detected at the age of 3 years without any extrarenal symptom. The pathological findings were examined, and targeted exome sequencing was performed. We also conducted reviews for all previously-reported cases of glomerulonephritis possessing FAT1 biallelic gene variants. We found two novel truncating variants in FAT1 (NM_005245.3), c.12867dup in exon 10, and, c.5480_5483del in exon 25. Our case showed mild proteinuria compared to previously-reported cases who showed SRNS and extrarenal symptoms that might have been because the latter variant in our patient was located on out of cadherin domains; however, our follow up period is short and we further need careful follow up. Our findings corroborate the evidence that individuals with FAT1-truncating variants can show isolated mild proteinuria. Further studies are needed to investigate the genotype–phenotype correlation in this disease. Therefore, our case will provide vital information regarding this rare condition. Keywords FAT-1 mutation · Steroid-resistant nephrotic syndrome
Introduction Nephrotic syndrome (NS) results in proteinuria, hypoalbuminemia, and edema. It is classified based on its response to steroid treatment into steroid-sensitive NS and steroid-resistant NS (SRNS) [1]. About 30% of SRNS cases are caused by monogenic gene variants, and in those cases, the risk of recurrence of SRNS after kidney transplantation is reduced * Rini Rossanti [email protected] 1
Department of Pediatrics, Kobe University Graduate School of Medicine, 7‑5‑1 Kusunoki‑cho, Chuo, Kobe, Hyogo 6500017, Japan
2
Department of Pediatrics, Fujioka General Hospital, Fujioka, Japan
3
Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Kobe, Japan
from 35 to 8% [2]. The first insights into the pathogenesis of SRNS were gained by the discovery of single-gene (monogenic) causes of SRNS, revealing that the encod
Data Loading...
