title: Point mutations causing the McLeod phenotype.
abstract: BACKGROUND
  The McLeod phenotype is defined by absence of Kx, weakening of Kell system antigens, and acanthocytosis. Individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities. Gene deletions, insertions, and point mutations that affect RNA splicing or that lead to premature stop codons have been reported to cause the McLeod phenotype. The McLeod phenotype may also be caused by mutations at a different splice site and by a novel mutation encoding an amino acid substitution that prevents transport to the cell surface.
  
  
  METHODS
  The coding and flanking intron regions of XK from four male, unrelated individuals with the McLeod phenotype and non-chronic granulomatous disease were sequenced and compared with the wild type sequence. Genomic DNA was amplified by PCR, and the products were sequenced. In one case, the mutant cDNA was expressed in a heterologous cell, and cell surface expression was determined.
  
  
  RESULTS
  Three individuals with the McLeod phenotype had mutations that disrupted conserved GT sequences present at RNA splice sites. Two of them had G>C mutations at the 5' splice site of intron 1, and one had a G>A mutation at the 5' splice site of intron 2. One person with the McLeod phenotype had a 746C>G mutation in exon 3 encoding an R222G substitution. In a transfected cell, the expressed protein from the latter mutant did not travel to the cell surface.
  
  
  CONCLUSIONS
  The McLeod phenotype may be caused by several different mutations.
authors.affiliation: Lindsley F. Kimball Research Institute, The New York Blood Center, New York, New York 10021, USA. drusso@nybc.org
authors.forename: David C W
authors.initials: DC
authors.lastname: Russo
authors.forename: Soohee
authors.initials: S
authors.lastname: Lee
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
authors.forename: Colvin M
authors.initials: CM
authors.lastname: Redman
mesh_terms: D000050:Acanthocytes; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D003062:Codon; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000276:immunology; D005091:Exons; D005838:Genotype; D006801:Humans; D007438:Introns; D007626:Kell Blood-Group System / Q000235:genetics*; D008297:Male; D009468:Neuromuscular Diseases / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D013577:Syndrome; D014162:Transfection; D014960:X Chromosome
chemical_list: D003062:Codon; D007626:Kell Blood-Group System; D004247:DNA