A novel frameshift mutation in the McLeod syndrome gene in a Japanese family

Hanaoka, Naoko; Yoshida, Katsumi; Nakamura, Akinori; Furihata, Kenichi; Seo, Taiko; Tani, Yoshihiko; Takahashi, Jun; Ikeda, Shu‐ichi; Hanyu, Norinao

doi:10.1016/s0022-510x(99)00028-3

Cited by 36 publications

(23 citation statements)

References 11 publications

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“…A marked reduction in glucose metabolism was also shown in the caudate and putamen of two affected brothers [14]. A positron-emission tomography study utilising 18 F-labelled dopa demonstrated reduced posterior putamen uptake comparable to levels seen in patients with idiopathic Parkinson's disease. This finding suggests that selective degeneration of dopaminergic projections between the nigra compacta and the posterior putamen may occur in neuroacanthocytosis [7,46].…”

Section: S Neuroimagingmentioning

confidence: 71%

Acanthocytosis and neurological disorders

Stevenson

Hardie

2001

Journal of Neurology

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Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.

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Section: S Neuroimagingmentioning

confidence: 71%

Acanthocytosis and neurological disorders

Stevenson

Hardie

2001

Journal of Neurology

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“…Several mutations abolishing or reducing XK mRNA splicing have been described, as have single base deletions and point mutations in the coding region leading to premature stop codons (6,(27)(28)(29)(30). The molecular defects causing the Ko phenotype have not been extensively studied, and only a recent report on a single Ko person with a 5Ј splice site defect has been described (31).…”

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confidence: 99%

Molecular Defects Underlying the Kell Null Phenotype

Lee¹,

Russo²,

Reiner³

et al. 2001

Journal of Biological Chemistry

121

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Expression of the Kell blood group system is dependent on two proteins, Kell and XK, that are linked by a single disulfide bond. Kell, a type II membrane glycoprotein, is a zinc endopeptidase, while XK, which has 10 transmembrane domains, is a putative membrane transporter. A rare phenotype termed Kell null (Ko) is characterized by the absence of Kell protein and Kell antigens from the red cell membrane and diminished amounts of XK protein. We determined the molecular basis of eight unrelated persons with Ko phenotypes by sequencing the coding and the intron-exon splice regions of KEL and, in some cases, analysis of mRNA transcripts and expression of mutants on the cell surface of transfected cells. Six subjects were homozygous: four with premature stop codons, one with a 5 splice site mutation, G to A, in intron 3, and one with an amino acid substitution (S676N) in exon 18. Two Ko persons with premature stop codons had identical mutations in exon 4 (R128Stop), another had a different mutation in exon 4 (C83Stop), and the fourth had a stop codon in exon 9 (Q348Stop). Two Ko persons were heterozygous for two mutations. One had a 5 splice site mutation (G to A) in intron 3 of one allele that caused aberrant splicing and exon skipping, and the other allele had an amino acid substitution in exon 10 (S363N). The other heterozygote had the same amino acid substitution in exon 10 (S363N) in one allele and a premature stop codon in exon 6 (R192Stop) in the other allele. The S363N and S676N mutants, expressed in 293T cells, were retained in a pre-Golgi compartment and were not transported to the cell surface, indicating that these mutations inhibit trafficking. We conclude that several different molecular defects cause the Kell null phenotype.

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“…Single case observations in the literature show that onset may range from 27 to 57 years. 9,10,[15][16][17][18][19][20] All neurologically documented cases of McLeod syndrome have shared limb chorea. In some, similar to our observations, the authors noted dystonic movements, 15 dysarthria, 16 and facial and generalized motor tics.…”

Section: Discussionmentioning

confidence: 99%

The chorea of McLeod syndrome

et al. 2001

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Among the movement disorders associated with acanthocytosis, McLeod syndrome (McKusick 314850) is the one that is best characterized on the molecular level. Its defining feature is low reactivity of Kell erythrocyte antigens. This is due to absence of membrane protein KX that forms a complex with the Kell protein. KX is coded for by the XK gene on the X-chromosome. We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome. The movement disorder commonly develops in the fifth decade and is progressive. It affects the limbs, the trunk and the face. In addition to facial grimacing, involuntary vocalization can be present. In early stages there may only be some restlessness or slight involuntary distal movements of ankles and fingers. Lip-biting and facial tics seem more common in autosomal recessive choreoacanthocytosis linked to chromosome 9. This, together with the absence of dysphagia in McLeod syndrome, may help in differential diagnosis. Recent findings suggest a role for the endothelin system of the striatum in the pathogenesis of McLeod syndrome.

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A novel frameshift mutation in the McLeod syndrome gene in a Japanese family

Cited by 36 publications

References 11 publications

Acanthocytosis and neurological disorders

Acanthocytosis and neurological disorders

Molecular Defects Underlying the Kell Null Phenotype

The chorea of McLeod syndrome

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