@entity8 (s) comprise a genetically heterogeneous group of conditions which include @entity3686 ( @entity3686 ) and @entity8 ( @entity8 ). Here we investigated 57 Greek-Cypriot families presenting glomerular microscopic @entity811 (GMH), with or without @entity644 or chronic kidney function decline, but excluded classical @entity3686 . We specifically searched the @entity19787 /A4 genes and identified 8 heterozygous mutations in 16 families (28,1%). Eight non-related families featured the founder mutation @entity19787 - @entity68718 . Renal biopsies from 8 @entity1 showed @entity8 and @entity628 ( @entity628 ). Ten @entity1 (11.5%) reached @entity454 ( @entity454 ) at ages ranging from 37-69-yo (mean 50,1-yo). Next generation sequencing of the @entity1 who progressed to @entity454 failed to reveal a second mutation in any of the @entity19787 / @entity68719 genes, supporting that true heterozygosity for @entity19787 /A4 mutations predisposes to @entity6192 / @entity454 . Although this could be viewed as a milder and late-onset form of autosomal dominant @entity3686 , we had no evidence of ultrastructural features or extrarenal manifestations that would justify this diagnosis. Functional studies in cultured podocytes transfected with wild type or mutant @entity19787 chains showed retention of mutant collagens and differential activation of the unfolded protein response (UPR) cascade. This signifies the potential role of the UPR cascade in modulating the final phenotype in @entity1 with collagen IV @entity8 .

Frequency of XXXX /COL4A4 Mutations amongst Families Segregating Glomerular Microscopic @entity811 and Evidence for Activation of the Unfolded Protein Response. Focal and Segmental Glomerulosclerosis Is a Frequent Development during Ageing.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity644 :: ('MESH:D011507', 'Disease') :: ['proteinuria'] @entity8 :: ('MESH:D007674', 'Disease') :: ['Familial glomerular hematuria', 'thin basement membrane nephropathy', 'nephropathies', 'TBMN'] @entity68719 :: ('28898;28884', 'Gene') :: ['A4/A5'] @entity3686 :: ('MESH:D009394', 'Disease') :: ['Alport Syndrome', 'AS'] @entity68718 :: ('p|SUB|G|1334|E', 'ProteinMutation') :: ['p.(G1334E)'] @entity628 :: ('MESH:D005923', 'Disease') :: ['FSGS', 'focal segmental glomerulosclerosis'] @entity19787 :: ('1285', 'Gene') :: ['COL4A3'] @entity811 :: ('MESH:D006417', 'Disease') :: ['hematuria'] @entity6192 :: ('1392', 'Gene') :: ['CRF'] @entity454 :: ('MESH:D007676', 'Disease') :: ['ESKD', 'end-stage kidney disease']
@entity19787 :: (1285,Gene) :: ['COL4A3']
