OBJECTIVE: To explore the genetic basis for a child featuring Chediak-Higashi syndrome (CHS). METHODS: Clinical manifestations and results of auxiliary examination of the proband were analyzed. The proband was subjected to whole exome sequencing, and the results were verified by Sanger sequencing. Correlation between the genotype and clinical phenotype was analyzed. RESULTS: The proband showed partial skin albinism, recurrent respiratory infection and other immune deficiencies. Genetic testing showed that he has harbored c.2437C>T (p.Arg813*) and c.6077dupA (p.Tyr2026fs) (NM_000081) compound heterozygous variants of the LYST gene, for which his parents were both carriers. Neither variant was reported previously. HEAT repeats domain was frequently associated with more severe phenotype of CHS (81.6%), whilst no variant has been found in the PH_BEACH domain. CONCLUSION This study has enriched the spectrum of LYST gene variants associated with CHS and enabled clinical diagnosis, prenatal diagnosis and prognostic evaluation for the child.
Male ; Humans ; Chediak-Higashi Syndrome/genetics* ; Vesicular Transport Proteins/genetics* ; Heterozygote ; Genetic Testing ; China

OBJECTIVE: To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation. METHODS: Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene. RESULTS: The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree. CONCLUSION Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.
Chediak-Higashi Syndrome ; genetics ; Exons ; Heterozygote ; Humans ; Mutation ; Pedigree ; Sequence Analysis, DNA ; Vesicular Transport Proteins ; genetics ; Whole Exome Sequencing

OBJECTIVETo explore the genetic basis for a pedigree affected with Chediak-Higashi syndrome (CHS).

METHODSClinical data of two CHS patients from the pedigree was collected and analyzed. Targeted next generation sequencing and Sanger sequencing were conducted to detect potential mutation of the LYST gene.

RESULTSBoth patients presented immunodeficiency, oculocutaneous albinism, and acidophilic inclusion body on bone marrow and blood smears. A homozygous c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both patients.

CONCLUSIONGenetic testing can play an important role in the diagnosis of CHS.

Chediak-Higashi Syndrome ; genetics ; Female ; Genetic Testing ; Humans ; Infant ; Infant, Newborn ; Mutation ; Pedigree ; Vesicular Transport Proteins ; genetics

To analyze the molecular mechanisms of cross-host transmission of the Aleutian mink disease vi rus (ADV), the hypervariable region fragment of the VP2 gene of the ADV in Jilin Province (China) was amplified. Sequencing analyses showed diversity at residue 174 by comparison with other VP2 genes in GenBank. The phylogenetic tree indicated that the ADV-JL strain had a close relationship with the highly pathogenic strain from Denmark: ADV-K. Results implied that residue 174 may be associated with ADV infectivity.
Aleutian Mink Disease ; virology ; Aleutian Mink Disease Virus ; chemistry ; classification ; genetics ; isolation & purification ; Amino Acid Sequence ; Animals ; Capsid Proteins ; chemistry ; genetics ; China ; Mink ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Sequence Analysis

Mink plasmacytosis, caused by Aleutian Mink Disease Virus (AMDV), poses a threat to the development of the animal fur industry. Neutralizing antibodies against AMDV may result in a persistent infection rather than providing protection for minks. To date,no specific methods to prevent or cure this disease have been developed. In order to eliminate mink plasmacytosis, antibody detection technology has been used globally as a dominant approach to screen for AMDV-positive minks. This paper introduces the classical technology, counterimmunoelectrophoresis and emerging technology in terms of AMDV antibody detection,and provides a glimpse into the future development of these technologies.
Aleutian Mink Disease ; diagnosis ; immunology ; virology ; Aleutian Mink Disease Virus ; immunology ; isolation & purification ; Animals ; Antibodies, Viral ; immunology ; Immunoassay ; instrumentation ; methods ; Mink

Aleutian mink disease parvovirus (AMDV) causes a persistent infection associated with immune complex disease, hypergammaglobulinemia, and high levels of antiviral antibodies. Despite the presence of an antibody, the virus is not cleared in vivo. Pre-existing antibodies may enhance viral infections, by Fc-receptor-mediated antibody-dependent enhancement (ADE), but the mechanism that underlies ADE has not been fully defined. Three models have been proposed, including: (1) interactions between antibody and FcR, complement C3 fragment and CR, or between C1q and C1qR, which promotes viral attachment to cells; (2) suppression of IFN-gamma-mediated host-cell antiviral gene expression by the upregulation of negative regulators of pathogen pattern recognition; and (3) the promotion of early IL-10 secretion. In addition, the role of cytokine IL-6 in ADE mediated disease development is discussed, to facilitate a better understanding of the pathogenesis of AMDV infection, as well as give insights into rational vaccine design approaches.
Aleutian Mink Disease ; immunology ; virology ; Aleutian Mink Disease Virus ; genetics ; immunology ; Animals ; Antibodies, Viral ; immunology ; Antibody-Dependent Enhancement ; Mink ; immunology ; virology

OBJECTIVETo establish a novel flow cytometry-based assay for measuring the expression of lysosomal-associated membrane protein 1 (LAMP-1, CD107α) on the cell surface of natural killer (NK) cells and cytotoxic T lymphocyte (CTL) and evaluate the screening value of this assay for cytotoxic defects-related diseases such as familial hemophagocytic lymphopro-liferative (FHL) syndrome.

METHODThree suspected Chediak-Higashi Syndrome (CHS) patients, three suspected FHL patients and 10 healthy children were enrolled in the study from October 2010 to June 2011. Their PBMCs were separated and activated overnight with IL-2. After the granule release of NK cells activated by phytohemagglutinin (PHA) and CD8+T cells by anti-CD3, the CD107α expression were analyzed by flow cytometry. The peripheral blood DNA and RNA of the patients were extracted to analyze the pathogenic genes via DNA-PCR/RT-PCR and direct sequencing.

RESULTThe CD107α expression on CTL in the ten healthy children significantly increased after activation by anti-CD3 [(0.18 ± 0.07)% vs. (4.47 ± 2.36)%, P < 0.05] and NK cells after activation by PHA [(0.27 ± 0.07)% vs. (5.80 ± 2.83)%, P < 0.05]. The frequency of CD107α-expression NK cells in three suspected CHS after activation was significantly elevated when compared with the healthy control [0.5%, 0.6% vs. (5.80 ± 2.83)%] except patient 2. After the anti-CD3 activation, the frequency of CD107α expression on CTL cells also showed no significant difference [0.3%, 0.9%, 0.2% vs. (4.47 ± 2.36)%] in three patients. All of their mean fluorescence intensity (MFI) showed the same trend. Patient 1 and 3 were identified to have LYST mutations (Patient 1: c.5411-5414 del TTTC, L1741fsX1758 and c.7975 C > T, R2596X; Patient 3: c.4863G > A, R1563H and c.5392-5393delAA, E1739fsX1756). There was no mutation identified in the LYST gene for patient 2. CD107α expression of NK cells and CTL in the suspected FHL patients and in mirror of these findings, no underlying gene variation of PRF, MUNC13-4 and STX11 were identified.

CONCLUSIONWe developed a method to quantitatively assess cytotoxicity of the NK cells and CTL by measuring the expression of CD107α on the cell membrane, which appeared to be an effective and rapid screening test for cytotoxic defects-related diseases such as FHL and other HLH secondary to primary immunodeficiency.

Case-Control Studies ; Cell Degranulation ; immunology ; Cell Membrane ; metabolism ; Chediak-Higashi Syndrome ; diagnosis ; genetics ; immunology ; metabolism ; Child, Preschool ; Cytotoxicity, Immunologic ; Female ; Flow Cytometry ; methods ; Humans ; Infant ; Interleukin-2 ; metabolism ; Killer Cells, Natural ; immunology ; metabolism ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; immunology ; metabolism ; Lysosomal-Associated Membrane Protein 1 ; metabolism ; Male ; Mutation ; Phytohemagglutinins ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

Bone Marrow Examination ; Chediak-Higashi Syndrome ; complications ; diagnosis ; pathology ; Cough ; etiology ; Diagnosis, Differential ; Fatal Outcome ; Female ; Fever ; etiology ; Humans ; Infant ; Leukocytes ; pathology

The patients is 6 years old girl, who was diagnosied Chediac-Higashi syndrome phase acceleration according to the following criteria:(1) Photophobia, partial oculocutaneous albinism, intermittent high febrile fine light light hair, hepatosplenomegaly (2) family past history: Consanguineous marriage (3) Giant granules within the bone marrow and peripheral blood granule leukocyte. The patient was responded to well with antibiotic, high dose C vitamin and corticoid. The diagnosis, treatment and Etiology of this sydrome are also discussed.
Chediak-Higashi Syndrome ; Case Reports [Publication Type]

No abstract available.
Chediak-Higashi Syndrome* ; Hyperpigmentation*