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Proteinuric renal disease v2.75 FAT1 Arina Puzriakova Tag gene-checked tag was added to gene: FAT1.
Proteinuric renal disease v1.226 FAT1 Eleanor Williams changed review comment from: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there is sufficient pedigrees and strong enough functional data to rate this gene green.; to: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there are sufficient pedigrees and strong enough functional data to rate this gene green.
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Classified gene: FAT1 as Green List (high evidence)
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. Despite concerns about possible variants in other genes in some pedigrees, and lower renal phenotype penetrance in others, it was considered that there is sufficient pedigrees and strong enough functional data to rate this gene green.
Proteinuric renal disease v1.85 FAT1 Eleanor Williams Gene: fat1 has been classified as Green List (High Evidence).
Proteinuric renal disease v1.84 FAT1 Eleanor Williams commented on gene: FAT1: After consultation with the GMS Renal Specialist Test group and comment from Moin Saleem, it was decided that there were enough patients from different pedigrees with nephrotic range proteinuria with rare FAT1 variants compatible with AR inheritance and that the biology is strong, as the KO mice get very severe nephrosis, and expression at the podocyte slit diaphragm, so that this gene should be rated green.
Proteinuric renal disease v1.59 FAT1 Eleanor Williams Phenotypes for gene: FAT1 were changed from to Glomerulotubular nephropathy
Proteinuric renal disease v1.58 FAT1 Eleanor Williams Publications for gene: FAT1 were set to
Proteinuric renal disease v1.57 FAT1 Eleanor Williams Mode of inheritance for gene: FAT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v1.56 FAT1 Eleanor Williams commented on gene: FAT1: Not associated with any phenotype in OMIM.

PMID: 26905694 - Gee et al 2016. 4 families reported with a variant in FAT1. 27 known genes previously linked to SRNS were screened in these individuals, but no explanatory mutations were detected. All affected individuals exhibited a glomerulotubular nephropathy of SRNS, tubular ectasia and microscopic haematuria among other phenotypes.

Family 1 - A4623, a Turkish boy from consanguineous parents with intellectual disability, pulmonary artery stenosis and bilateral blepharoptosis in early childhood, admitted to the hospital at age 15 years because of proteinuria and haematuria. Kidney biopsy showed a glomerulotubular nephropathy. Following WES and filtering of variants from normal reference sequence, 3 rare variants in FAT1, PIDD and DZIP1 remained. The variant in the FAT1 gene, is a homozygous protein truncating mutation (c.3093_3096del, p.P1032Cfs*11). This variant is classified as a VUS in OMIM.

Family 2 One child of Arab origin (A3027) presented with proteinuria and haematuria. A3027 was diagnosed with Ewing sarcoma, and lung and spinal metastasis at the age of 15 years. Following variant filtering by HM and WES, two rare missense variants in FAT1 and EHD1 remained . Mutations in the 27 known SRNS genes were excluded by evaluation of the WES data. The variant (c.857A>F;p.N286S) in FAT1 is reported as a SNP in the dbSNP database, however, its minor allele frequency is 0.0002 and it never occurred in the homozygous state. The FAT1 variant alters an amino-acid residue conserved throughout evolution down to Drosophila melanogaster.

Families 3 and 4 - When performing highly parallel sequencing of all FAT1 exons in 1,500 additional individuals with features of NS and 800 individuals with features of tubulointerstitial nephroapathy, we detected in 2 additional families. . In a female African-American girl (A789) from non-consanguineous parents, another compound-heterozygous mutation was detected (c.3008C>T, p.A1003V and c.9259C>G, p. R3087G). Further information was not available and segregation analysis was not performed since the girl was lost for follow-up. A3507, an African girl from non-consanguineous parents, showed haematuria and proteinuria at the age of 2 years. One of the compound-heterozygous mutation (c.4517G>A, p.R1506H) was detected in her mother, but not the other. DNA from the father was not available.

Functional studies indicate an absence of FAT1 in patient fibroblasts (from family 1) and decreased migration rates compared to controls. Knockdown of FAT1 in differentiated podocytes showed similarly decreased migration rates, which were associated with decreased active RAC1 and CDC42, implicating a defect in RHO GTPase signaling in the pathogenesis.
Proteinuric renal disease v1.16 FAT1 Eleanor Williams reviewed gene: FAT1: Rating: GREEN; Mode of pathogenicity: ; Publications: PMID: 26905694; Phenotypes: Glomerulotubular nephropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Proteinuric renal disease v1.15 FAT1 Eleanor Williams gene: FAT1 was added
gene: FAT1 was added to Proteinuric renal disease. Sources: NHS GMS
Mode of inheritance for gene: FAT1 was set to