title: Mutation in alpha 5(IV) collagen chain gene in nonfamilial hematuria.
abstract: Alport syndrome is an inherited disorder characterized by progressive nephritis with ultrastructural basket-weave changes of the glomerular basement membrane and neurosensory deafness. Mutations in the COL4A5 gene encoding the Type IV collagen alpha 5 chain have been reported to occur in patients with X-linked Alport syndrome. A girl with hematuric nephritis, characteristic basket-weave glomerular basement membrane changes, and abnormal expression of the Type IV collagen alpha 5 chain immunohistochemically, but no family history of nephritis, was identified. Mutation detection enhancement gel electrophoresis of the polymerase chain reaction-amplified exons of COL4A5 from this patient revealed a sequence variant in the exon 50 region. Sequence analysis of her polymerase chain reaction product demonstrated a single-base (C; nucleotide 4728 from the 5' end) deletion in exon 50. This novel mutation alters the reading frame and introduces a translation stop codon that would be expected to result in a noncollagenous domain with only 209, instead of the normal 229, amino acid residues. Gene tracking with restriction enzyme AfIIII demonstrated that her mother was normal. These findings represent a new mutation of the X-linked Alport syndrome in this patient and demonstrate that a COL4A5 gene mutation causes the abnormal expression of Type IV collagen alpha 5 chain protein.
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: H
authors.initials: H
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Sado
authors.forename: K
authors.initials: K
authors.lastname: Sano
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D001483:Base Sequence; D001485:Basement Membrane / Q000648:ultrastructure; D002648:Child; D003094:Collagen / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005091:Exons; D005260:Female; D006417:Hematuria / Q000235:genetics*; D006801:Humans; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009154:Mutation; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014960:X Chromosome
chemical_list: D003094:Collagen; D004247:DNA