Chs syndrome
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Chediak-Higashi Syndrome: Genetic and Clinical Insights
Overview of Chediak-Higashi Syndrome (CHS)
Chediak-Higashi Syndrome (CHS) is a rare, autosomal recessive disorder characterized by severe immunologic deficiencies, hypopigmentation, and progressive neurological dysfunction. The hallmark of CHS is the presence of giant organelles and granules in various cell types, resulting from defective protein trafficking necessary for the normal function of these cytoplasmic components1 2 4.
Genetic Basis of CHS
CHS1 Gene and Mutations
The CHS1 gene, also known as LYST, has been identified as the gene responsible for CHS. Mutations in this gene lead to the production of a dysfunctional protein, which is crucial for the proper formation and function of lysosomes and other organelles. The CHS1 gene is located on chromosome 1q42-q44 and encodes a protein that is 3801 amino acids long1 2 4. Mutations such as frameshifts and nonsense mutations in the CHS1 gene result in truncated, non-functional proteins, leading to the clinical manifestations of CHS1 7.
Homology with the Beige Mouse
The beige mouse serves as an animal model for CHS due to its similar genetic and phenotypic characteristics. The beige gene (Lyst) in mice is homologous to the human CHS1 gene, and both share significant sequence homology. This homology has facilitated the identification and study of the CHS1 gene in humans2 4 9.
Clinical Manifestations
Immunologic Deficiencies
Patients with CHS exhibit severe immunologic deficiencies, including neutropenia, impaired chemotaxis, and defective natural killer (NK) cell function. These deficiencies lead to recurrent infections and an increased susceptibility to pyogenic bacteria2 4 6.
Neurological Dysfunction
Neurological involvement in CHS is variable but often includes peripheral neuropathy and progressive neurological decline. The accelerated phase of CHS, characterized by lymphohistiocytic infiltration of multiple organs, resembles lymphoma and is a significant cause of mortality4 6 7.
Hypopigmentation and Bleeding Tendencies
CHS is also characterized by hypopigmentation, resulting in oculocutaneous albinism, and a tendency to bruise easily due to deficient platelet dense bodies. These features are a direct consequence of the defective lysosomal trafficking in melanocytes and platelets4 6 7.
Diagnosis and Management
Diagnostic Criteria
Diagnosis of CHS is based on clinical features, genetic testing for CHS1 mutations, and the presence of giant granules in granulocytes and other cell types. High-resolution genetic mapping and homozygosity mapping have been instrumental in identifying the CHS1 gene and its mutations1 2 10.
Treatment Approaches
There is no specific cure for CHS, and treatment is primarily supportive. Bone marrow transplantation (BMT) is the only curative treatment option and is recommended before the onset of the accelerated phase. Without BMT, most patients succumb to infections or complications from the accelerated phase4 6 9.
Conclusion
Chediak-Higashi Syndrome is a complex genetic disorder with significant clinical implications. Advances in genetic research have elucidated the role of the CHS1 gene and its mutations in the pathogenesis of the disease. Despite the lack of a specific cure, early diagnosis and bone marrow transplantation can significantly improve outcomes for affected individuals. Further research is essential to develop targeted therapies and improve the quality of life for patients with CHS.
Sources and full results
Most relevant research papers on this topic
Mutations in the Chediak-Higashi syndrome gene (CHS1) indicate requirement for the complete 3801 amino acid CHS protein.
The functional CHS protein is a 3801 amino acid polypeptide encoded by a 13.5 kb mRNA, supporting our assertion that the CHS gene is a key gene in Chediak-Higashi syndrome.
Case Report
Highly CitedIdentification and mutation analysis of the complete gene for Chediak–Higashi syndrome
The complete gene for Chediak-Higashi syndrome has been identified, revealing pathologic mutations and a modular architecture similar to yeast vacuolar sorting protein VPS15.
Highly CitedUpdate on cerebral hyperperfusion syndrome
Cerebral hyperperfusion syndrome (CHS) is a complex and unpredictable syndrome after revascularization procedures, with its underlying mechanism still not fully understood and diverse diagnostic criteria.
Literature ReviewHighly CitedClinical, molecular, and cell biological aspects of Chediak-Higashi syndrome.
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, bruisability, bleeding, recurrent infections, and neurologic involvement, with the LYST gene on chromosome 1q42 being the identified
Highly CitedCerebral hyperperfusion syndrome
Cerebral hyperperfusion syndrome (CHS) occurs in 0-3% of patients after carotid endarterectomy and can lead to severe complications if not treated early and effectively.
Highly CitedAnalysis of the Lysosomal Storage Disease Chediak–Higashi Syndrome
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder affecting humans, mice, and other mammals, with the CHS gene being the responsible gene and cellular alterations observed in mutant cells.
Highly CitedTwo novel CHS1 (LYST) mutations: clinical correlations in an infant with Chediak-Higashi syndrome.
Two novel CHS1 gene mutations in an infant with Chediak-Higashi syndrome result in truncated proteins, potentially leading to severe phenotypes and requiring allogeneic hematopoietic stem cell transplantation.
Case ReportClinical characteristics and outcomes of chédiak–Higashi syndrome: A nationwide survey of Japan
Chédiak-Higashi syndrome (CHS) in Japan is characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism, with various phenotypes reported.
Observational StudyGenetic Defects in Chediak–Higashi Syndrome and the beige Mouse
The human CHS1 gene and mouse beige gene are homologous, potentially facilitating research and development of novel treatments for Chediak-Higashi syndrome.
Highly CitedHomozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg).
The human CHS gene is likely homologous to mouse bg, mapping to an 18.8-cM interval in chromosome segment 1q42-q44.
Observational Study