This report describes Chediak-Higashi syndrome (CHS), a lysosomal storage disorder; CHS is inherited as an autosomal recessive. The human gene implicated in this disease is LYST, which encodes Lysosomal Trafficking Regulator, a protein that regulates intracellular protein trafficking in endosomes. There is a single fly ortholog, mv, for which loss-of-function mutations, RNAi-targeting constructs, and an allele caused by insertional mutagenesis have been generated.
The human gene has not been reported to have been introduced into flies.
Loss-of-function mutations in the Dmel\mv gene result in an eye color phenotype resulting from oversized pigment granules, an immune deficiency phenotype and enlarged lysosome-related organelles. Physical interactions of the mv protein product have been described; see below and in the gene report for Dmel\mv.
[updated Jul. 2017 by FlyBase; FBrf0222196]
[CHEDIAK-HIGASHI SYNDROME; CHS](https://omim.org/entry/214500)
[LYSOSOMAL TRAFFICKING REGULATOR; LYST](https://omim.org/entry/606897)
Chediak-Higashi syndrome (CHS) is a rare disorder characterized by oculocutaneous albinism, immunodeficiency, and problems with blood clotting. Starting in infancy, frequent severe infections (most commonly bacterial) occur and are usually infections of the skin and upper respiratory tract. In ~85% of individuals, a life-threatening accelerated phase develops which is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure and is caused by lymphoproliferative infiltration of the bone marrow and reticuloendothelial system. Neurologic symptoms may appear anytime from childhood to early adulthood and may include cognitive impairment, parkinsonism, ataxia, and peripheral neuropathy. [from Gene Reviews, http://www.ncbi.nlm.nih.gov/books/NBK5188/ 2016.2.29 and Gene Cards, http://www.genecards.org/cgi-bin/carddisp.pl?gene=LYST 2016.2.29]
The features of Chediak-Higashi syndrome are partial albinism, photophobia, nystagmus, large eosinophilic, peroxidase-positive inclusion bodies in the myeloblasts and promyelocytes of the bone marrow, neutropenia, abnormal susceptibility to infection, and peculiar malignant lymphoma. [from MIM:214500, 2016.2.29]
CHS is caused by mutations in the LYST gene, which encodes a lysosomal trafficking regulator. [from MIM:214500, 2016.2.26]
The main cellular characteristic of CHS is enlarged lysosomes or lysosome-related organelles. [from Gene Reviews, http://www.ncbi.nlm.nih.gov/books/NBK5188/ 2016.2.29]
Mutations in the LYST gene impair the normal function of the encoded lysosomal trafficking regulator protein, which disrupts the size, structure, and function of lysosomes and related structures in cells throughout the body. [from Genetics Home Reference, GHR:condition:chediak-higashi-syndrome 2016.2.29]
LYST may be required for sorting endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules. [from Gene Cards, http://www.genecards.org/cgi-bin/carddisp.pl?gene=LYST 2016.2.29]
Mutations in the lysosomal trafficking regulator gene LYST result in defective membrane targeting of the proteins present in secretory lysosomes. [from MIM:214500, 2016.2.26]
One to one: 1 human to 1 Drosophila.
Ortholog of human LYST (1 Drosophila to 1 human). Dmel\mv shares 23% identity and 37% similarity with human LYST.
