title: Natural history of genetically proven autosomal recessive Alport syndrome.
abstract: BACKGROUND
  Autosomal recessive Alport syndrome (ARAS) is a rare hereditary disease caused by homozygous or compound heterozygous mutations in either the COL4A3 or COL4A4 genes. Failure to diagnose ARAS cases is common, even if detailed clinical and pathological examinations are carried out. As the mutation detection rate for ARAS is unsatisfactory, we sought to develop more reliable diagnostic methods and provide a better description of the clinicopathological characteristics of this disorder.
  
  
  METHODS
  A retrospective analysis of 30 genetically diagnosed patients with ARAS in 24 pedigrees was conducted. The mutation detection strategy comprised three steps: (1) genomic DNA analysis using polymerase chain reaction (PCR) and direct sequencing; (2) mRNA analysis using reverse transcription (RT)-PCR to detect RNA processing abnormalities; (3) semi-quantitative PCR using capillary electrophoresis to detect large heterozygous deletions.
  
  
  RESULTS
  Using the three-step analysis, we identified homozygous or compound heterozygous mutations in all patients. Interestingly, 20% of our ARAS patients showed normal expression of α5 in kidney tissue. The median age of developing end-stage renal disease was 21 years.
  
  
  CONCLUSIONS
  The strategy described in this study improves the diagnosis for ARAS families. Although immunohistochemical analysis of α5 can provide diagnostic information, normal distribution does not exclude the diagnosis of ARAS.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo, Kobe, Hyogo, 6500017, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Oka
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Fu
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hashimura
authors.forename: Naoya
authors.initials: N
authors.lastname: Morisada
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Yan
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Igor
authors.initials: I
authors.lastname: Vorechovsky
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D009394:Nephritis, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D055815:Young Adult