title: McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement.
abstract: BACKGROUND
  The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with hematologic, neuromuscular, and central nervous system (CNS) manifestations. All carriers of the McLeod blood group phenotype examined so far had at least subclinical signs of systemic involvement.
  
  
  METHODS
  Evaluation of two brothers carrying the McLeod phenotype with neurologic examination, immunohematology, RBC membrane protein Western blotting, analysis of XK DNA sequence and RNA levels, muscle histology including XK/Kell immunohistochemistry, cerebral magnetic resonance imaging (MRI), and quantified positron emission tomography (PET).
  
  
  RESULTS
  Immunohematology and Western blotting confirmed presence of the McLeod blood group phenotype. No acanthocytosis or other hematologic anomalies were found. XK gene sequence analysis revealed a missense mutation in exon 3 (E327K). WBC XK RNA levels were not decreased. There were no neuromuscular and CNS signs or symptoms. In addition, no subclinical involvement was discovered on the basis of normal muscle histology with a physiologic pattern of XK and Kell immunohistochemistry, normal cerebral MRI, and quantified PET.
  
  
  CONCLUSIONS
  Known disease-causing XK gene mutations comprised deletions, nonsense, or splice-site mutations predicting absent or truncated XK protein devoid of the Kell-protein binding site. Although the E327K missense mutation was associated with the immunohematologic characteristics of McLeod syndrome, the mutated XK protein seemed to be largely functional. These findings contribute to the understanding of the physiology of XK and Kell proteins, and the pathogenetic mechanisms of acanthocytosis, myopathy, and striatal neurodegeneration in McLeod syndrome.
authors.affiliation: Department of Neurology and the Institutes of Neuropathology, Nuclear Medicine, and Neuroradiology, University Hospital Zürich, Switzerland. hans.jung@nos.usz.ch
authors.forename: Hans H
authors.initials: HH
authors.lastname: Jung
authors.forename: Martin
authors.initials: M
authors.lastname: Hergersberg
authors.forename: Marco
authors.initials: M
authors.lastname: Vogt
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.forename: Valerie
authors.initials: V
authors.lastname: Treyer
authors.forename: Benno
authors.initials: B
authors.lastname: Röthlisberger
authors.forename: Spyros S
authors.initials: SS
authors.lastname: Kollias
authors.forename: David
authors.initials: D
authors.lastname: Russo
authors.forename: Beat M
authors.initials: BM
authors.lastname: Frey
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D015153:Blotting, Western; D001927:Brain Diseases / Q000175:diagnosis / Q000235:genetics; D002819:Chorea / Q000235:genetics*; D041321:Chromosomes, Human, X; D008040:Genetic Linkage; D006402:Hematologic Diseases / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007626:Kell Blood-Group System / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D020125:Mutation, Missense; D009468:Neuromuscular Diseases / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D014055:Tomography, Emission-Computed
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D007626:Kell Blood-Group System; D012333:RNA, Messenger; C087883:XK protein, human