title: Clinical and histological findings of autosomal dominant renal-limited disease with LMX1B mutation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Konomoto
authors.affiliation: Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Imamura
authors.affiliation: Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Orita
authors.affiliation: Department of Pediatrics, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moritake
authors.affiliation: Dialysis Division, University of Miyazaki Hospital, Miyazaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Dialysis Division, University of Miyazaki Hospital, Miyazaki, Japan.|Department of Haemovascular Medicine and Artificial Organs, University of Miyazaki, Miyazaki, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Fujimoto
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hisano
authors.affiliation: Department of Human Genetics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.affiliation: Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism; 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 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D009401:Nephrosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009402:Nephrosis, Lipoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D011507:Proteinuria / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D003094:Collagen
keywords: LMX1B; autosomal dominant; nail-patella syndrome; podocin; whole exome sequencing