BACKGROUND: McLeod syndrome is a rare X-linked neuroacanthocytosis syndrome with 
hematologic, muscular, and neurologic manifestations. McLeod syndrome is caused 
by mutations in the XK gene whose product is expressed at the red blood cell 
(RBC) surface but whose function is currently unknown. A variety of XK mutations 
has been reported but no clear phenotype-genotype correlation has been found, 
especially for the point mutations affecting splicing sites.
STUDY DESIGN AND METHODS: A man suspected of neuroacanthocytosis was evaluated 
by neurologic examination, electromyography, muscle biopsy, muscle computed 
tomography, and cerebral magnetic resonance imaging. The McLeod RBC phenotype 
was disclosed by blood smear and immunohematology analyses and then confirmed at 
the biochemical level by Western blot analysis. The responsible XK mutation was 
characterized at the mRNA level by reverse transcription-polymerase chain 
reaction (PCR), identified by genomic DNA sequencing, and verified by 
allele-specific PCR.
RESULTS: A novel XK splice site mutation (IVS1-1G>A) has been identified in a 
McLeod patient who has developed hematologic, neuromuscular, and neurologic 
symptoms. This is the first reported example of a XK point mutation affecting 
the 3' acceptor splice site of Intron 1, and it was demonstrated that this 
mutation indeed induces aberrant splicing of XK RNA and lack of XK protein at 
the RBC membrane.
CONCLUSION: The detailed characterization at the molecular biology level of this 
novel XK splice site mutation associated with the clinical description of the 
patient contributes to a better understanding of the phenotype-genotype 
correlation in the McLeod syndrome.