Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation.
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.


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.


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.


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.
['Konomoto|Takao|T|', 'Imamura|Hideaki|H|', 'Orita|Mayuko|M|', 'Tanaka|Etsuko|E|', 'Moritake|Hiroshi|H|', 'Sato|Yuji|Y|', 'Fujimoto|Shouichi|S|', 'Harita|Yutaka|Y|', 'Hisano|Satoshi|S|', 'Yoshiura|Koh-Ichiro|K|', 'Nunoi|Hiroyuki|H|']
D000293:Adolescent D000328:Adult D001706:Biopsy D002648:Child D002675:Child, Preschool D003094:Collagen D004252:DNA Mutational Analysis D018450:Disease Progression D005260:Female D005455:Fluorescent Antibody Technique D005819:Genetic Markers D020022:Genetic Predisposition to Disease D005923:Glomerulosclerosis, Focal Segmental D006579:Heterozygote D006801:Humans D007223:Infant D007668:Kidney D007676:Kidney Failure, Chronic D060850:LIM-Homeodomain Proteins D008297:Male D009154:Mutation D009401:Nephrosis D009402:Nephrosis, Lipoid D010375:Pedigree D010641:Phenotype D011507:Proteinuria D013997:Time Factors D014157:Transcription Factors D055815:Young Adult
autosomal dominant LMX1B nail-patella syndrome whole exome sequencing podocin