The Apical Endocytic-Lysosomal Apparatus in CLCN5 Mutations with Phenotypic-Genotypic Correlations in Three Cases.
Int J Mol Sci
; 25(2)2024 Jan 12.
Article
in En
| MEDLINE
| ID: mdl-38256038
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glomerulosclerosis, Focal Segmental
/
Lysosomes
Limits:
Humans
/
Male
Language:
En
Journal:
Int J Mol Sci
/
Int. j. mol. sci. (Online)
/
International journal of molecular sciences (Online)
Year:
2024
Document type:
Article
Affiliation country:
Hungary
Country of publication:
Switzerland