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McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement.
- Source :
-
Transfusion [Transfusion] 2003 Jul; Vol. 43 (7), pp. 928-38. - Publication Year :
- 2003
-
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.<br />Study Design and 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).<br />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.<br />Conclusion: 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.
- Subjects :
- Blotting, Western
Brain Diseases diagnosis
Brain Diseases genetics
Chromosomes, Human, X
Genetic Linkage
Hematologic Diseases diagnosis
Hematologic Diseases genetics
Humans
Immunohistochemistry
Magnetic Resonance Imaging
Male
Middle Aged
Muscle, Skeletal pathology
Neuromuscular Diseases diagnosis
Neuromuscular Diseases genetics
Pedigree
Polymorphism, Genetic
RNA, Messenger analysis
Reverse Transcriptase Polymerase Chain Reaction
Syndrome
Tomography, Emission-Computed
Amino Acid Transport Systems, Neutral genetics
Chorea genetics
Kell Blood-Group System genetics
Mutation, Missense
Phenotype
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1132
- Volume :
- 43
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Transfusion
- Publication Type :
- Academic Journal
- Accession number :
- 12823753
- Full Text :
- https://doi.org/10.1046/j.1537-2995.2003.t01-1-00434.x