title: Immunohistochemical and molecular genetic evidence for type IV collagen alpha5 chain abnormality in the anterior lenticonus associated with Alport syndrome.
abstract: OBJECTIVE
  To present evidence for a type IV collagen alpha5 chain (alpha5[IV]) abnormality in the anterior lens capsule of a patient with anterior lenticonus associated with Alport syndrome.
  
  
  METHODS
  The anterior lens capsule obtained from a 54-year-old man with anterior lenticonus associated with Alport syndrome was examined ultrastructurally and stained immunohistochemically for the alpha chains of type IV collagen, alpha1(IV) to alpha6(IV). A search was also made for a mutation in the COL4A5 complementary DNA encoding the alpha5(IV) chain by reverse transcription-polymerase chain reaction of illegitimate transcripts.
  
  
  RESULTS
  The anterior lens capsule of the patient was much thinner than that of normal subjects and lacked the alpha3(IV) to alpha6(IV) chains immunohistochemically, while control specimens stained positively for all of the alpha(IV) chains. The patient had a C-to-T transition at nucleotide 5231 causing a nonsense mutation, R1677X, in the COL4A5 complementary DNA.
  
  
  CONCLUSIONS
  Our findings demonstrated that normal anterior lens capsules express all of the alpha(IV) chains and that a patient with anterior lenticonus associated with Alport syndrome had a mutation in the COL4A5 gene resulting in the lack of immunoreactivity to alpha3(IV) to alpha6(IV) chains in the anterior lens capsule. Clinical Relevance This study showed abnormal composition of alpha(IV) chains in the anterior lens capsule of a patient with anterior lenticonus caused by a nonsense mutation in the COL4A5 gene. Further investigation of the phenotype-genotype relationship will provide a better understanding of the molecular pathogenesis of anterior lenticonus.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Science, Kanazawa University, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohkubo
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takeda
authors.forename: Tomomi
authors.initials: T
authors.lastname: Higashide
authors.forename: Mari
authors.initials: M
authors.lastname: Ito
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sakurai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shirao
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Oda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
mesh_terms: D002387:Cataract Extraction; D018389:Codon, Nonsense; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007903:Lens Capsule, Crystalline / Q000378:metabolism* / Q000648:ultrastructure; D007905:Lens Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D024141:Collagen Type IV; D020033:Protein Isoforms