Chorea-acanthocytosis: Genetic linkage to chromosome 9q21

Justin P. Rubio, Adrian Danek, Caroline Stone, Richard Chalmers, Nicholas Wood, Christine Verellen, Xavier Ferrer, Alessandro Malandrini, Gian M. Fabrizi, Michela Manfredi, Jefferey Vance, Margaret Pericak-Vance, Robert D Jr. Brown, Gabrielle Rudolf, Fabienne Picard, Elisa Alonso, Mitchell Brin, Andrea H. Németh, Martin Farrall, Anthony P. Monaco

Research output: Contribution to journalArticle

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Abstract

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (Θ = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.

Original languageEnglish (US)
Pages (from-to)899-908
Number of pages10
JournalAmerican Journal of Human Genetics
Volume61
Issue number4
StatePublished - Oct 1997
Externally publishedYes

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Neuroacanthocytosis
Genetic Linkage
Abetalipoproteinemia
Chromosomes
Cytogenetics
Organism Cloning
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Rubio, J. P., Danek, A., Stone, C., Chalmers, R., Wood, N., Verellen, C., ... Monaco, A. P. (1997). Chorea-acanthocytosis: Genetic linkage to chromosome 9q21. American Journal of Human Genetics, 61(4), 899-908.

Chorea-acanthocytosis : Genetic linkage to chromosome 9q21. / Rubio, Justin P.; Danek, Adrian; Stone, Caroline; Chalmers, Richard; Wood, Nicholas; Verellen, Christine; Ferrer, Xavier; Malandrini, Alessandro; Fabrizi, Gian M.; Manfredi, Michela; Vance, Jefferey; Pericak-Vance, Margaret; Brown, Robert D Jr.; Rudolf, Gabrielle; Picard, Fabienne; Alonso, Elisa; Brin, Mitchell; Németh, Andrea H.; Farrall, Martin; Monaco, Anthony P.

In: American Journal of Human Genetics, Vol. 61, No. 4, 10.1997, p. 899-908.

Research output: Contribution to journalArticle

Rubio, JP, Danek, A, Stone, C, Chalmers, R, Wood, N, Verellen, C, Ferrer, X, Malandrini, A, Fabrizi, GM, Manfredi, M, Vance, J, Pericak-Vance, M, Brown, RDJ, Rudolf, G, Picard, F, Alonso, E, Brin, M, Németh, AH, Farrall, M & Monaco, AP 1997, 'Chorea-acanthocytosis: Genetic linkage to chromosome 9q21', American Journal of Human Genetics, vol. 61, no. 4, pp. 899-908.
Rubio JP, Danek A, Stone C, Chalmers R, Wood N, Verellen C et al. Chorea-acanthocytosis: Genetic linkage to chromosome 9q21. American Journal of Human Genetics. 1997 Oct;61(4):899-908.
Rubio, Justin P. ; Danek, Adrian ; Stone, Caroline ; Chalmers, Richard ; Wood, Nicholas ; Verellen, Christine ; Ferrer, Xavier ; Malandrini, Alessandro ; Fabrizi, Gian M. ; Manfredi, Michela ; Vance, Jefferey ; Pericak-Vance, Margaret ; Brown, Robert D Jr. ; Rudolf, Gabrielle ; Picard, Fabienne ; Alonso, Elisa ; Brin, Mitchell ; Németh, Andrea H. ; Farrall, Martin ; Monaco, Anthony P. / Chorea-acanthocytosis : Genetic linkage to chromosome 9q21. In: American Journal of Human Genetics. 1997 ; Vol. 61, No. 4. pp. 899-908.
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AU - Danek, Adrian

AU - Stone, Caroline

AU - Chalmers, Richard

AU - Wood, Nicholas

AU - Verellen, Christine

AU - Ferrer, Xavier

AU - Malandrini, Alessandro

AU - Fabrizi, Gian M.

AU - Manfredi, Michela

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AU - Pericak-Vance, Margaret

AU - Brown, Robert D Jr.

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AU - Picard, Fabienne

AU - Alonso, Elisa

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AU - Németh, Andrea H.

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AU - Monaco, Anthony P.

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