Anu Leinonen's research while affiliated with Kansas City VA Medical Center and other places

... The translated product consists of 1685 amino acid residues, including a signal peptide of 26 residues, a collagenous domain of 1430 residues encoded by exons 2-47, which begins with a noncollagenous sequence of 14 residues, and a gly-Xaa-Yaa-repeat sequence interrupted at 22 locations. This is followed by a carboxyl-terminal non-collagenous domain of 229 residues encoded by exons 47-51 [16]. The main genetic pattern of AS caused by the COL4A5 mutation is X-linked dominant inheritance. ...

... We consider the BM matrigel density used in in vitro invasion assays reported in [2], whose authors estimated a protein concentration of about 10 mg/ml. Considering a molecular weight in the typical weight range of collagen IV, the main component of the ECM found in the BM, i.e. about 160kDa [75], we compute M max = 10 mg/ml 160 × 10 3 Da ≈ 6.2510 −5 mol/dm 3 = 62.5 × 10 3 nM. ...

... The analysis of the minigene demonstrated an anomalous splicing pattern, leading to the deletion of 14 amino acids within the Gly-X-Y repetition portion of the long central trihelix domain of the α3(IV) chain. Consequently, the anticipated outcome is producing a shortened α3(IV) chain, eliminating four Gly-X-Y sequences [18] . This is consistent with earlier deletion reports within the collagen domain framework [19] . ...

... Alport syndrome (AS) is an inherited renal disease caused by variants in COL4A3, COL4A4, or COL4A5 gene [1][2][3]. The clinical manifestations of Alport syndrome include hematuria, proteinuria, and progressive renal failure, sometimes accompanied by hearing loss and ocular lesions [4]. ...

... La forma X -linked è secondaria alla presenza di varianti anomale del gene COL4A5 mappato sul cromosoma X, che codifica per la catena alfa-5(IV) del collagene IV [14]. Tale forma si associa sovente ad una storia familiare di ematuria (associata o meno a proteinuria) e insufficienza renale progressiva. ...

... De novo glycine-XY mutations are less frequent than other de novo mutations (5.5 vs 13.9%). This is in contrast to the fact that glycine-XY substitutions are the most common mutation in AS (40%) [53]. The later onset of renal failure may increase the fitness of reproduction in these patients resulting in an evolutionary advantage. ...

... The same heterozygous missense mutation of ATP7B was detected in his parents and younger brother ( Figure 3B). This p. Gly573Asp variant in the COL4A5 gene has been reported previously (13). It is listed in the Human Gene Mutation Database (HGMD) and is believed to cause AS (accession number CM983307). ...

... Anti-glomerular basement membrane (GBM) disease is an autoimmune disease, and the primary target of circulating and in situ bound antibody is the non-collagenous (NC) 1 domain of the a3 chain of type IV collagen. [1,2] This antigen is known as the Goodpasture antigen, and the anti-GBM autoantibodies not only damage the glomerular GBM, resulting in rapidly progressive glomerulonephritis with crescent formation via the ruptured GBM, but also disrupt the alveolar basement membrane, resulting in pulmonary hemorrhaging. Patients with Goodpasture syndrome have autoantibodies against Goodpasture antigens, including a3 (IV) NC1 domain, a1 (IV) NC1 and a4 (IV) NC1 at frequencies of 80%, 15% and 4%, respectively. ...

... It has been demonstrated that IgG anti-a3(IV)NC1 antibodies recognized 2 major conformational epitopes, designated as EA and EB. 12 On Western-blot analysis, sera possessing IgA anti-a3(IV)NC1 antibodies also recognized a3 chain under nonreducing condition. Therefore, we speculated that these IgA antibodies might also recognize the same conformational epitopes of EA and EB. ...

... The major target antigen of anti-GBM autoantibodies is the non-collagen domain(NC1) of α3 chain of type IV collagen[α3(IV)NC1] 2 , located in both GBM and alveolar basement membrane. Two conformational epitopes on α3(IV)NC1 has been identified, designated as EA and EB[3][4][5] .Most patients with anti-GBM disease undergo rapidly deteriorating kidney dysfunction, and frequently concurrent diffuse alveolar hemorrhage. However, due to its rare occurrence of 0.5~1 person per million per year, the kidney pathological studies of this severe disease are relatively limited. ...