title: Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV α5 chain.
abstract: X-linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the type IV collagen α5 chain (α5(IV)). Complete absence of α5(IV) in the renal basal membrane is considered a pathological characteristic in male patients; however, positive α5(IV) staining has been found in over 20% of patients. We retrospectively studied 52 genetically diagnosed male X-linked Alport syndrome patients to evaluate differences in clinical characteristics and renal outcomes between 15 α5(IV)-positive and 37 α5(IV)-negative patients. Thirteen patients in the α5(IV)-positive group had non-truncating mutations consisting of nine missense mutations, three in-frame deletions, and one splice-site mutation resulting in small in-frame deletions of transcripts. The remaining two showed somatic mutations with mosaicism. Missense mutations in the α5(IV)-positive group were more likely to be located before exon 25 compared with missense mutations in the α5(IV)-negative group. Furthermore, urinary protein levels were significantly lower and the age at onset of end-stage renal disease was significantly higher in the positive group than in the negative group. These results help to clarify the milder clinical manifestations and molecular characteristics of male X-linked Alport syndrome patients expressing the α5(IV) chain.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hashimura
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Fu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ohtsubo
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Oka
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ninchoji
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Ishimori
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Morisada
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Matsunoshita
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kamiyoshi
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000032:analysis / Q000235:genetics*; D018450:Disease Progression; D005091:Exons; D020022:Genetic Predisposition to Disease; D050533:Glomerular Basement Membrane / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism; D008297:Male; D009030:Mosaicism; D009154:Mutation; D020125:Mutation, Missense; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D017384:Sequence Deletion; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV