BACKGROUND: McLeod neuroacanthocytosis syndrome is a late-onset X-linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype-genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. STUDY DESIGN AND METHODS: Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. RESULTS: Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. CONCLUSIONS: The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.
BACKGROUND:McLeod neuroacanthocytosis syndrome is a late-onset X-linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype-genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. STUDY DESIGN AND METHODS: Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. RESULTS: Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. CONCLUSIONS: The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.
Authors: Lucia De Franceschi; Giovanni Scardoni; Carlo Tomelleri; Adrian Danek; Ruth H Walker; Hans H Jung; Benedikt Bader; Sara Mazzucco; Maria Teresa Dotti; Angela Siciliano; Antonella Pantaleo; Carlo Laudanna Journal: PLoS One Date: 2012-02-15 Impact factor: 3.240