title: A new point mutation in the COL4A5 gene described in a Spanish family with X-linked Alport syndrome.
abstract: OBJECTIVE
  Alport syndrome is a hereditary glomerulonephritis, X-linked in 85% of the cases. This form is associated with mutations in the COL4A5 gene which encodes the alpha5 chain of type IV collagen. We have performed the mutational analysis of the COL4A5 gene in a Spanish family with X-linked Alport syndrome.
  
  
  METHODS
  We have analyzed three polymorphic markers close to the gene to confirm the X chromosome linkage. By means of the PCR technique, we have screened the 51 exons of the gene.
  
  
  RESULTS
  The segregation of the alleles from the analyzed markers was in agreement with the X linkage. Direct sequencing of PCR-amplified products has shown a CCT-to-CTT change in exon 25, resulting in substitution of a proline for a leucine at position 619 of the polypeptide chain (nucleotide 2058).
  
  
  CONCLUSIONS
  Although proline is considered a nonconserved amino acid, it is essential, upon hydroxylation, in the maintenance of a stable alpha chain triple-helix collagen. Furthermore, the change cosegregates with the disease in all affected members of the family, not being present in 80 control chromosomes. This represents a new mutation in the COL4A5 gene found in the Spanish population.
authors.affiliation: Centre d'Investigacions en Bioquímica i Biologia Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Palenzuela
authors.forename: Lluís
authors.initials: L
authors.lastname: Callís
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilalta
authors.forename: Angel
authors.initials: A
authors.lastname: Vila
authors.forename: José L
authors.initials: JL
authors.lastname: Nieto
authors.forename: Anna
authors.initials: A
authors.lastname: Meseguer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D013030:Spain; D014960:X Chromosome / Q000235:genetics*
chemical_list: D024141:Collagen Type IV