Localization of the giant axonal neuropathy gene to chromosome 16q24

Kevin M. Flanigan, Thomas Owen Crawford, John W. Griffin, Hans H. Goebel, Alfried Kohlschütter, Judith Ranells, Peter R. Camfield, Louis J. Ptáček

Research output: Contribution to journalArticle

Abstract

Giant axonal neuropathy (GAN) is a degenerative disorder of the peripheral nerves that is inherited as an autosomal recessive trait, p resenting in early childhood and progressing to death, usually by late adolescence. Diagnosis is made by peripheral nerve biopsy, in which a striking pathological finding is seen-fibers distorted by giant axonal swellings filled with densely packed bundles of neurofilaments (the primary intermediate filament in neurons), with segregation of other axoplasmic organelles. In addition to disorganized neurofilaments in nerve, disorganization of other members of the intermediate filament family of proteins is seen in other tissues; this implies that the underlying defect is one of generalized intermediate filament organization, with neurofilaments predominantly affected. We have pursued a genomewide search for regions of homozygosity of descent in 5 consanguineous families. A 5.3-cM region of homozygosity, shared in all 5 families, was found on chromosome 16q24, and linkage was established to this locus with a LOD score of 4.18 at θ = 0.00 at the most tightly linked marker, D16S3098. Determination of this locus is the first step toward characterizing the gene responsible for a fundamental property of intermediate filament organization and may shed light on other disorders (such as amyotrophic lateral sclerosis) in which neurofilament pathology is prominent.

Original languageEnglish (US)
Pages (from-to)143-148
Number of pages6
JournalAnnals of Neurology
Volume43
Issue number1
DOIs
StatePublished - Jan 1998

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Giant Axonal Neuropathy
Intermediate Filaments
Chromosomes
Genes
Peripheral Nerves
Organizations
Intermediate Filament Proteins
Amyotrophic Lateral Sclerosis
Organelles
Pathology
Biopsy
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Flanigan, K. M., Crawford, T. O., Griffin, J. W., Goebel, H. H., Kohlschütter, A., Ranells, J., ... Ptáček, L. J. (1998). Localization of the giant axonal neuropathy gene to chromosome 16q24. Annals of Neurology, 43(1), 143-148. https://doi.org/10.1002/ana.410430126

Localization of the giant axonal neuropathy gene to chromosome 16q24. / Flanigan, Kevin M.; Crawford, Thomas Owen; Griffin, John W.; Goebel, Hans H.; Kohlschütter, Alfried; Ranells, Judith; Camfield, Peter R.; Ptáček, Louis J.

In: Annals of Neurology, Vol. 43, No. 1, 01.1998, p. 143-148.

Research output: Contribution to journalArticle

Flanigan, KM, Crawford, TO, Griffin, JW, Goebel, HH, Kohlschütter, A, Ranells, J, Camfield, PR & Ptáček, LJ 1998, 'Localization of the giant axonal neuropathy gene to chromosome 16q24', Annals of Neurology, vol. 43, no. 1, pp. 143-148. https://doi.org/10.1002/ana.410430126
Flanigan KM, Crawford TO, Griffin JW, Goebel HH, Kohlschütter A, Ranells J et al. Localization of the giant axonal neuropathy gene to chromosome 16q24. Annals of Neurology. 1998 Jan;43(1):143-148. https://doi.org/10.1002/ana.410430126
Flanigan, Kevin M. ; Crawford, Thomas Owen ; Griffin, John W. ; Goebel, Hans H. ; Kohlschütter, Alfried ; Ranells, Judith ; Camfield, Peter R. ; Ptáček, Louis J. / Localization of the giant axonal neuropathy gene to chromosome 16q24. In: Annals of Neurology. 1998 ; Vol. 43, No. 1. pp. 143-148.
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