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Clinical, molecular, and cell biological aspects of Chediak-Higashi syndrome.

Abstract：

:Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by variable degrees of oculocutaneous albinism, easy bruisability, and bleeding as a result of deficient platelet dense bodies, and recurrent infections, with neutropenia, impaired chemotaxis and bactericidal activity, and abnormal NK cell function. Neurologic involvement is variable, but often includes peripheral neuropathy. Most patients also undergo an "accelerated phase," which is a nonmalignant lymphohistiocytic infiltration of multiple organs resembling lymphoma. Death often occurs in the first decade from infection, bleeding, or development of the accelerated phase. The hallmark of CHS is the presence of huge cytoplasmic granules in circulating granulocytes and many other cell types. These granules are peroxidase-positive and contain lysosomal enzymes, suggesting that they are giant lysosomes or, in the case of melanocytes, giant melanosomes. The underlying defect in CHS remains elusive, but the disorder can be considered a model for defects in vesicle formation, fusion, or trafficking. Because the beige mouse demonstrates many characteristics similar to those of human CHS patients, including dilution of coat color, recurrent infections, and the presence of giant granules, it is considered the animal homologue of CHS. The beige gene, Lyst, was mapped and sequenced in 1996, prompting identification of the human LYST gene on chromosome 1q42. Lyst and LYST show 86.5% sequence homology. LYST encodes a 429 kDa protein with a function that remains unknown, but the source of extensive speculation among students of cell biology.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Introne W,Boissy RE,Gahl WA

doi

10.1006/mgme.1999.2927

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

283-303

issue

2

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(99)92927-X

journal_volume

68

pub_type

杂志文章,评审

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