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Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation.
- Source :
-
Nephrology (Carlton, Vic.) [Nephrology (Carlton)] 2016 Sep; Vol. 21 (9), pp. 765-73. - Publication Year :
- 2016
-
Abstract
- Aim: Mutations of LMX1B cause nail-patella syndrome, a rare autosomal dominant disorder. Recently, LMX1B R246Q heterozygous mutations were recognised in nephropathy without extrarenal manifestation. The aim of this study was to clarify characteristics of nephropathy caused by R246Q mutation.<br />Methods: Whole exome sequencing was performed on a large family with nonsyndromic autosomal dominant nephropathy without extrarenal manifestation. Clinical and histological findings of patients with LMX1B mutation were investigated.<br />Results: LMX1B R246Q heterozygous mutation was identified in five patients over three generations. Proteinuria or haematoproteinuria was recognized by urinary screening from all patients in childhood. Proteinuria gradually increased to nephrotic levels and renal function decreased in adolescence. Two patients progressed to end-stage renal disease in adulthood. Renal histology demonstrated minimal change in childhood and focal segmental glomerulosclerosis in adulthood. Using electron microscopy, focal collagen deposition could be detected in glomeruli even when a "moth-eaten appearance" was not apparent in the glomerular basement membrane. In addition, podocin expression in glomerular podocytes was significantly decreased, even in the early stages of disease progression.<br />Conclusion: Comprehensive genetic analyses and collagen or tannic acid staining may be useful for diagnosis of LMX1B-associated nephropathy. While renal prognosis of R246Q may be worse than that of typical NPS nephropathy, signs of podocytopathy can be detected during the infantile period; thus, childhood urinary screening may facilitate early detection.<br /> (© 2015 Asian Pacific Society of Nephrology.)
- Subjects :
- Adolescent
Adult
Biopsy
Child
Child, Preschool
Collagen metabolism
DNA Mutational Analysis
Disease Progression
Female
Fluorescent Antibody Technique
Genetic Markers
Genetic Predisposition to Disease
Glomerulosclerosis, Focal Segmental metabolism
Glomerulosclerosis, Focal Segmental pathology
Heterozygote
Humans
Infant
Kidney metabolism
Kidney physiopathology
Kidney Failure, Chronic pathology
Kidney Failure, Chronic physiopathology
Male
Nephrosis pathology
Nephrosis physiopathology
Nephrosis, Lipoid metabolism
Nephrosis, Lipoid pathology
Pedigree
Phenotype
Proteinuria pathology
Proteinuria physiopathology
Time Factors
Young Adult
Glomerulosclerosis, Focal Segmental genetics
Kidney pathology
Kidney Failure, Chronic genetics
LIM-Homeodomain Proteins genetics
Mutation
Nephrosis genetics
Nephrosis, Lipoid genetics
Proteinuria genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1797
- Volume :
- 21
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nephrology (Carlton, Vic.)
- Publication Type :
- Academic Journal
- Accession number :
- 26560070
- Full Text :
- https://doi.org/10.1111/nep.12666