TY  - JOUR
AV  - public
N2  - Dent disease type 1 is characterized by pathogenic CLCN5 gene variants and impaired receptor-mediated endocytosis in proximal tubules. However, mutation-related abnormalities in proximal tubules have not yet been described. Here, we present three patients with CLCN5 alterations and distinct morphological changes of the apical endocytic-lysosomal apparatus. The proximal tubular ultrastructure was investigated in kidney biopsy samples of three boys genotyped for non-nephrotic proteinuria. Controls: seven patients with nephrotic-range glomerular proteinuria. The genotyping findings revealed an already-known missense mutation in one patient and hitherto undescribed frameshift variants in two patients. Low-molecular-weight proteinuria, focal global glomerulosclerosis, proximal tubular changes, and tubular calcium deposits characterized each case. Three subsets of proximal tubular cells were observed: those without any abnormality, those with aplasia of apical endocytic-lysosomal apparatus and shrinkage of cells, and those with hypoplasia of apical endocytic apparatus, accumulation of proteinaceous substance in dysmorphic lysosomes, and dysmorphic mitochondria. The distribution of subsets varied from patient to patient. In one patient with a frameshift variant, an oxidative stress-like injury of proximal tubular cells and podocytes accompanied the above-mentioned alterations. Focal aplasia/hypoplasia of apical endocytic apparatus and subsequent changes in cytoplasmic organelles characterized proximal tubules in the CLCN5 pathogenic variants.
VL  - 25
UR  - https://doi.org/10.3390/ijms25020966
Y1  - 2024///
IS  - 2
ID  - publicatio35413
A1  -  Kalmár Tibor
A1  -  Jakab Dániel
A1  -  Maróti Zoltán
A1  -  Lakatos Orsolya Judit
A1  -  Vas Tibor
A1  -  Bereczki Csaba
A1  -  Iványi Béla
EP  - 16
TI  - The Apical Endocytic-Lysosomal Apparatus in CLCN5 Mutations with Phenotypic-Genotypic Correlations in Three Cases : [Case report]
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
SN  - 1661-6596
N1  - * Megosztott szerz?ség

Szövegében 3 oldalnál hosszabb esetismertetés, ezért besorolása szakcikk az MTA V. Osztályának ajánlása alapján. (zr, SZTE admin5, 2024-09-10)
ER  -