Genomes and Genes
chediak higashi syndrome
Summary: A form of phagocyte bactericidal dysfunction characterized by unusual oculocutaneous albinism, high incidence of lymphoreticular neoplasms, and recurrent pyogenic infections. In many cell types, abnormal lysosomes are present leading to defective pigment distribution and abnormal neutrophil functions. The disease is transmitted by autosomal recessive inheritance and a similar disorder occurs in the beige mouse, the Aleutian mink, and albino Hereford cattle.
- Manoli I, Golas G, Westbroek W, Vilboux T, Markello T, Introne W, et al. Chediak-Higashi syndrome with early developmental delay resulting from paternal heterodisomy of chromosome 1. Am J Med Genet A. 2010;152A:1474-83 pubmed publisher..Unmasking of a separate autosomal recessive cause of developmental delay, or an additive effect of the paternal heterodisomy, could underlie the severity of the phenotype in this patient. ..
- Martín Fernández J, Cabanillas J, Rivero Carmena M, Lacasa E, Pardo J, Anel A, et al. Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes. J Leukoc Biol. 2005;77:661-8 pubmed..We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation. ..
- Westbroek W, Adams D, Huizing M, Koshoffer A, Dorward H, Tinloy B, et al. Cellular defects in Chediak-Higashi syndrome correlate with the molecular genotype and clinical phenotype. J Invest Dermatol. 2007;127:2674-7 pubmed
- Jin Y, Zhang L, Wang S, Chen F, Gu Y, Hong E, et al. Whole Genome Sequencing Identifies Novel Compound Heterozygous Lysosomal Trafficking Regulator Gene Mutations Associated with Autosomal Recessive Chediak-Higashi Syndrome. Sci Rep. 2017;7:41308 pubmed publisher..The present study contributes to improved understanding of the causes of this disease and provides new ideas for possible treatments. ..
- Faigle W, Raposo G, Tenza D, Pinet V, Vogt A, Kropshofer H, et al. Deficient peptide loading and MHC class II endosomal sorting in a human genetic immunodeficiency disease: the Chediak-Higashi syndrome. J Cell Biol. 1998;141:1121-34 pubmed..These results suggest that the product of the Lyst gene is required for sorting endosomal resident proteins into late multivesicular endosomes by a mechanism involving microtubules. ..
- Wang X, Herberg F, Laue M, Wullner C, Hu B, Petrasch Parwez E, et al. Neurobeachin: A protein kinase A-anchoring, beige/Chediak-higashi protein homolog implicated in neuronal membrane traffic. J Neurosci. 2000;20:8551-65 pubmed
- Pratt H, Carroll R, Jones J, Lothrop C. Platelet aggregation, storage pool deficiency, and protein phosphorylation in mice with Chediak-Higashi syndrome. Am J Vet Res. 1991;52:945-50 pubmed..Results indicate that the biochemical defect(s) in platelet function in beige mice is partially attributable to storage pool deficiency and does not result in an absolute defect in phosphorylation of 40- and 20-kD proteins. ..
- Clark R, Griffiths G. Lytic granules, secretory lysosomes and disease. Curr Opin Immunol. 2003;15:516-21 pubmed..However, studies of this disease reveal differences between the various different types of secretory lysosomes, including lytic granules...
- Trambas C, Griffiths G. Delivering the kiss of death. Nat Immunol. 2003;4:399-403 pubmed..Although the process by which this occurs is not yet known, it is possible that events taking place at the immunological synapse may render the killer cell susceptible to fratricidal attack by other killer cells...
- Certain S, Barrat F, Pastural E, Le Deist F, Goyo Rivas J, Jabado N, et al. Protein truncation test of LYST reveals heterogenous mutations in patients with Chediak-Higashi syndrome. Blood. 2000;95:979-83 pubmed..Different LYST mutations were identified in all subjects through this approach, strengthening the observation of a high frequency of truncated LYST proteins as the genetic cause of CHS. ..
- Schmitz G, Schambeck C. Molecular defects in the ABCA1 pathway affect platelet function. Pathophysiol Haemost Thromb. 2006;35:166-74 pubmed..It is concluded that the presence of ABCA1 and ABCG1 in the AP-3 pathway will have major impact for membrane phospholipid processing and HDL metabolism and their relation to disorders of lysosome-related organelles...
- Holt O, Gallo F, Griffiths G. Regulating secretory lysosomes. J Biochem. 2006;140:7-12 pubmed..The different regulatory components seem to vary from one cell type to another, providing a multitude of ways for fine tuning the release of secretory lysosomes...
- Honda N, Ohnishi K, Fujishiro T, Ikeda M, Ito K. Alteration of release and role of adenosine diphosphate and thromboxane A2 during collagen-induced aggregation of platelets from cattle with Chediak-Higashi syndrome. Am J Vet Res. 2007;68:1399-406 pubmed..Furthermore, results of the study reported here indicated that TXA(2) was important for aggregation of bovine platelets. ..
- Premalata C, Devi L, Madhumathi D, Appaji L. Chediak-Higashi syndrome masquerading as acute leukemia: the significance of lymphocyte inclusions. J Clin Oncol. 2006;24:3505-7 pubmed
- Kypri E, Schmauch C, Maniak M, De Lozanne A. The BEACH protein LvsB is localized on lysosomes and postlysosomes and limits their fusion with early endosomes. Traffic. 2007;8:774-83 pubmed..These results support the model that LvsB and Lyst proteins act as negative regulators of fusion by limiting the heterotypic fusion of early endosomes with postlysosomal compartments. ..
- Jogl G, Shen Y, Gebauer D, Li J, Wiegmann K, Kashkar H, et al. Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain. EMBO J. 2002;21:4785-95 pubmed..Functional studies in intact cells demonstrate the requirement of both the PH and the BEACH domains for activity. A prominent groove at the interface between the two domains may be used to recruit their binding partners. ..
- Lem L, Riethof D, Scidmore Carlson M, Griffiths G, Hackstadt T, Brodsky F. Enhanced interaction of HLA-DM with HLA-DR in enlarged vacuoles of hereditary and infectious lysosomal diseases. J Immunol. 1999;162:523-32 pubmed..These findings suggest a mechanism for perturbation of Ag presentation by class II molecules and consequent immune deficiencies in both diseases. ..
- Rath S, Jain V, Marwaha R, Trehan A, Rajesh L, Kumar V. Griscelli syndrome. Indian J Pediatr. 2004;71:173-5 pubmed..Initially a possibility of Chediak Higashi syndrome (CHS) was considered, but a negative investigative work up prompted us to look for an alternate diagnosis...
- Valente N, Machado M, Boggio P, Alves A, Bergonse F, Casella E, et al. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo). 2006;61:327-32 pubmed..We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available. ..
- Khocht A, Viera Negron Y, Ameri A, Abdelsayed R. Periodontitis associated with Chediak-Higashi syndrome in a young African American male. J Int Acad Periodontol. 2010;12:49-55 pubmed..Due to the weakened immunity of CHS patients, periodontal management is usually unsuccessful. Tooth extractions are recommended to eliminate the periodontal problems and reduce the risk of fatal bacterial infections. ..
- Ahluwalia J, Pattari S, Trehan A, Marwaha R, Garewal G. Accelerated phase at initial presentation: an uncommon occurrence in Chédiak-Higashi syndrome. Pediatr Hematol Oncol. 2003;20:563-7 pubmed..This case underscores the importance of a bone marrow examination in patients with unusual presentations of rare disorders. ..
- Oetting W. Albinism. Curr Opin Pediatr. 1999;11:565-71 pubmed..Analysis of mutations in these seven genes has revealed that the phenotypic spectrum associated with albinism is broad, making molecular analysis an important part in the accurate diagnosis of this disease...
- Oliver C, Essner E. Formation of anomalous lysosomes in monocytes, neutrophils, and eosinophils from bone marrow of mice with Chédiak-Higashi syndrome. Lab Invest. 1975;32:17-27 pubmed..As a result of the continued lysosomal fusion, the mature monocytes, neutrophils, and eosinophils from the beige mouse contained fewer but often greatly enlarged lysosomes. ..
- Ruiz Maldonado R. Hypomelanotic conditions of the newborn and infant. Dermatol Clin. 2007;25:373-82, ix pubmed..These, and examples of less frequent hypopigmentations are briefly discussed in this article. A new classification for depigmented nevi is also proposed. ..
- Jacobi C, Koerner C, Fruehauf S, Rottenburger C, Storch Hagenlocher B, Grau A. Presynaptic dopaminergic pathology in Chediak-Higashi syndrome with parkinsonian syndrome. Neurology. 2005;64:1814-5 pubmed
- Trigg M, Schugar R. Chédiak-Higashi syndrome: hematopoietic chimerism corrects genetic defect. Bone Marrow Transplant. 2001;27:1211-3 pubmed..Hematopoietic chimerism offers a cure with a potential reduction in the side-effects that result from marrow transplantation and the associated preparative therapies. ..
- Nargund A, Madhumathi D, Premalatha C, Rao C, Appaji L, Lakshmidevi V. Accelerated phase of chediak higashi syndrome mimicking lymphoma--a case report. J Pediatr Hematol Oncol. 2010;32:e223-6 pubmed publisherb>Chediak Higashi Syndrome (CHS) is a rare autosomal recessive disease, characterized by partial oculocutaneous albinism, frequent pyogenic infections, and the presence of abnormal large granules in leukocytes and other granule containing ..
- Dinauer M. Disorders of neutrophil function: an overview. Methods Mol Biol. 2007;412:489-504 pubmed publisher..Diagnostic tests and treatment approaches are also summarized for each neutrophil disorder. ..
- Prueitt J, Chi E, Lagunoff D. Pulmonary surface-active materials in the Chediak-Higashi syndrome. J Lipid Res. 1978;19:410-5 pubmed..The quantity of surface-active material phospholipid recovered in the lavage of beige mouse lungs was normal. The basis for the abnormal accumulation of lamellar body lipids is not known. ..
- Ahluwalia J, Kumar V, Trehan A, Marwaha R, Garewal G. The psuedo-Chediak-Higashi anomaly: an unusual staining pattern in an Indian child with acute myeloid leukemia. Pediatr Hematol Oncol. 2004;21:199-202 pubmed..On remission, these granules were no longer seen. To the best of the authors' knowledge, this pattern of staining has not been previously reported in the literature. ..
- Gebauer D, Li J, Jogl G, Shen Y, Myszka D, Tong L. Crystal structure of the PH-BEACH domains of human LRBA/BGL. Biochemistry. 2004;43:14873-80 pubmed..The structure suggests intimate association between the PH and the BEACH domains, and surface plasmon resonance studies confirm that the two domains of the protein FAN have high affinity for each other, with a K(d) of 120 nM. ..
- Kaplan J, De Domenico I, Ward D. Chediak-Higashi syndrome. Curr Opin Hematol. 2008;15:22-9 pubmed..Understanding the basic mechanisms that govern vesicle trafficking will provide essential information regarding how loss of CHS1/LYST affects hematologic, immunologic and neurologic processes. ..
- Gunay Aygun M, Huizing M, Gahl W. Molecular defects that affect platelet dense granules. Semin Thromb Hemost. 2004;30:537-47 pubmed..The gene products involved in these disorders help elucidate the generalized process of the formation of vesicles from extant membranes such as the Golgi. ..
- Swank R, Brandt E. Turnover of kidney beta-glucuronidase in normal and Chédiak-Higashi (beige) mice. Am J Pathol. 1978;92:755-72 pubmed..The altered secretion of lysosomal enzymes from specific kidney cells of beige mice may serve as a model system for study of defective fusion of lysosomes with phagocytosed bacteria in cells of Chédiak-Higashi patients. ..
- Cui S, Tanabe F, Terunuma H, Iwatani Y, Nunoi H, Agematsu K, et al. A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity. Clin Exp Immunol. 2001;125:283-90 pubmed..These results suggest an association between ceramide-induced PKC down-regulation and the cellular dysfunctions in CHS. ..
- Cowles B, Meyers K, Wardrop K, Menard M, Sylvester D. Prolonged bleeding time of Chediak-Higashi cats corrected by platelet transfusion. Thromb Haemost. 1992;67:708-12 pubmed
- Elin R, Edelin J, Wolff S. Infection and immunoglobulin concentrations in Chediak-Higashi mice. Infect Immun. 1974;10:88-91 pubmed..CHS mice have an increased susceptibility to pyogenic infections, which is not due to immunoglobulin deficiency. These mice may provide a useful laboratory model for the study of increased susceptibility to infection. ..
- Nualart Grollmus Z, Morales Chávez M, Silvestre Donat F. Periodontal disease associated to systemic genetic disorders. Med Oral Patol Oral Cir Bucal. 2007;12:E211-5 pubmed
- Yamakuchi H, Agaba M, Hirano T, Hara K, Todoroki J, Mizoshita K, et al. Chediak-Higashi syndrome mutation and genetic testing in Japanese black cattle (Wagyu). Anim Genet. 2000;31:13-9 pubmed..This mutation is the most likely cause of CHS in Wagyu cattle. In addition, we describe quick, inexpensive, PCR based tests that will permit elimination of the CHS mutation from Wagyu breeding herds. ..
- Oliver J. Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. Am J Pathol. 1976;85:395-418 pubmed..Similarly, granule morphology appeared normal in peripheral blood leukocytes from mice treated chronically in vivo with cholinergic agonists. ..
- Golovleva I, Hultdin J, Roos G, Wahlin A, Holmgren G. Co-existence of pseudo-Chediak-Higashi anomaly and double minutes containing C-MYC oncogene in three patients with AML M2. Leukemia. 2002;16:152-4 pubmed
- Ganschow R, Grabhorn E, Lemke J, Lepler R. Cardiac failure in an infant with Chediak-Higashi syndrome: a hypothesis of the effect of diadenosine polyphosphates. Pediatr Allergy Immunol. 2002;13:307-10 pubmed..Our hypothesis requires further investigation in other patients. ..
- Mori M, Yamasaki K, Nakanishi S, Kitada K, Higuchi K, Namiki C, et al. A new beige mutant rat ACI/N-Lystbg-Kyo. Exp Anim. 2003;52:31-6 pubmed..Further characterization of the ACI/N-Lystbg-Kyo rats should make it useful as an animal model for human Chediak-Higashi syndrome. ..
- Habermehl P, Althoff S, Knuf M, Höpner J. [Griscelli syndrome: a case report]. Klin Padiatr. 2003;215:82-5 pubmed..The finding of grey hairs in childhood should alert clinicians to consider Griscelli syndrome since an early diagnosis is life and health saving. ..
- Colgan S, Hull Thrall M, Gasper P, Gould D, Rose B, Fulton R, et al. Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation. Bone Marrow Transplant. 1991;7:365-74 pubmed..Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats. ..
- Meyers K, Costa J, Magnuson J. Compartmentation of 4,6-difluoro-5HT studied by nuclear magnetic resonance in normal and CHS bovine platelets. Thromb Res. 1990;58:265-72 pubmed
- Kreiter S, Winkelmann N, Schneider P, Schuler M, Fischer T, Ullmann A, et al. Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation. Bone Marrow Transplant. 2001;28:157-61 pubmed..Predominant donor T cell chimerism is not a prerequisite for initial allogeneic hematopoietic proliferation. However for sustained long-term engraftment it is of major importance. ..
- Huizing M, Helip Wooley A, Westbroek W, Gunay Aygun M, Gahl W. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359-86 pubmed publisher..We also summarize the function, composition, and resident cell types of the major LROs. Finally, we describe the clinical characteristics of the major human LRO disorders. ..
- Shiraishi M, Kawashima S, Moroi M, Shin Y, Morita T, Horii Y, et al. A defect in collagen receptor-Ca2+ signaling system in platelets from cattle with Chediak-Higashi syndrome. Thromb Haemost. 2002;87:334-41 pubmed..These results suggest that a defect in the rhodocytin-sensitive pathway is responsible for decreasing the response to collagen in CHS platelets. It remains to be determined which receptor is associated with the mechanism. ..
- Ozaki K, Fujimori H, Nomura S, Nishikawa T, Nishimura M, PanHou H, et al. Morphologic and hematologic characteristics of storage pool deficiency in beige rats (Chédiak-Higashi syndrome of rats). Lab Anim Sci. 1998;48:502-6 pubmed..Electron microscopy revealed that platelets had fewer dense granules, whereas other organelles had normal structure. This morphologic and functional evidence confirms that platelets of beige rats have the typical characteristics of SPD. ..
- Jayaranee S, Menaka N. Chediak-Higashi syndrome: a case report. Malays J Pathol. 2004;26:53-7 pubmed
- Kawa K. [Contribution of Japanese researchers to progress in the field of hematology: Chediak-Higashi syndrome]. Nihon Naika Gakkai Zasshi. 2002;91:2047-9 pubmed