Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome.
Mutations in either the COL4A3 or the COL4A4 genes, encoding the alpha3 and alpha4 chains of type IV collagen, are responsible for the autosomal-recessive form of Alport syndrome, a progressive hematuric nephropathy characterized by glomerular basement membrane abnormalities. Reported here are the complete COL4A3 exon-intron structure and a comprehensive screen for mutations of the 52 COL4A3 exons in 41 unrelated patients diagnosed as having autosomal Alport syndrome. This resulted in the identification of 21 mutations that are expected to be causative. Furthermore, it is shown that heterozygous COL4A3 missense mutations, when symptomatic, can be associated with a broad range of phenotypes, from familial benign hematuria to the complete features of Alport syndrome nephropathy.
Heidet
Laurence
L
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Arrondel
Christelle
C
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Forestier
Lionel
L
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Cohen-Solal
Lola
L
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Mollet
Geraldine
G
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Gutierrez
Bruno
B
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Stavrou
Christophoros
C
Renal Unit, Paphos General Hospital, Paphos, Cyprus.
Gubler
Marie Claire
MC
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
Antignac
Corinne
C
INSERM U423, Université René Descartes, Hôpital Necker-Enfants Malades, Paris, France.
D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D003094:Collagen