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Localization of the giant axonal neuropathy gene to chromosome 16q24
Author(s) -
Flanigan Kevin M.,
Crawford Thomas O.,
Griffin John W.,
Goebel Hans H.,
Kohlschütter Alfried,
Ranells Judith,
Camfield Peter R.,
Ptáček Louis J.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410430126
Subject(s) - neurofilament , intermediate filament , locus (genetics) , biology , pathology , amyotrophic lateral sclerosis , genetics , gene , medicine , disease , cytoskeleton , immunohistochemistry , cell
Giant axonal neuropathy (GAN) is a degenerative disorder of the peripheral nerves that is inherited as an autosomal recessive trait, presenting 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.