Chediak-Higashi syndrome

Talbert, Malissa; Malicdan, May Christine V.; Introne, Wendy J.

doi:10.1097/moh.0000000000000766

Cited by 7 publications

(3 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gene is located on the long arm of chromosome 1 [1q42-43]. Around 40 different mutations have been discovered, including nonsense and missense mutations, deletions, and insertions [4][5].…”

Section: Introductionmentioning

confidence: 99%

Chédiak Higashi Syndrome -A hematological Diagnosis and Review of Literature

Raj¹,

Aden²

2023

J Pathol Res Rev Rep

View full text Add to dashboard Cite

Chediak Higashi Syndrome is a rare autosomal recessive disease come in picture early in age, mainly paediatric group and is fatal. In India, till the year 2000, only five cases have been reported. In this study ,we present all the cases reported in India, their clinical presentation, CBC ,PBS ,Bone marrow findings, skin biopsy or hair study (if performed) and their correlation to see the accelerated phase of the disease and approach to the management. Determined peripheral blood smear examination is the key to arrest the diagnosis of Chediak Higashi Syndrome in developing country like India, defining it is the most easiest, quickest, cheap, easily available investigation in our country.

show abstract

Section: Introductionmentioning

confidence: 99%

Chédiak Higashi Syndrome -A hematological Diagnosis and Review of Literature

Raj¹,

Aden²

2023

J Pathol Res Rev Rep

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

“…LYST, a multidomain protein implicated in various aspects of vesicular trafficking, affects lysosome morphology and function (28, 29). Pathogenic LYST variants are linked with Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and congenital immunodeficiency (30, 31). Moreover, CHS and some LYST variants are associated with risk for hemophagocytic lymphohistiocytosis (HLH), a severe (often fatal) systemic disorder characterized by hyperinflammation (32, 33).…”

mentioning

confidence: 99%

A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome

Khan,

Ji,

Guzman-Rivera

et al. 2024

Preprint

View full text Add to dashboard Cite

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.

show abstract

Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia

Ronchini,

Gigli,

Fontanini

et al. 2024

Cancer Reports

View full text Add to dashboard Cite

BackgroundMyeloid neoplasms, including acute myeloid leukemia, have been traditionally among the less investigated cancer types concerning germline predisposition. Indeed, myeloid neoplasms with germline predisposition are challenging to identify because often display similar clinical and morphological characteristics of sporadic cases and have similar age at diagnosis. However, a misidentifications of familiarity in myeloid neoplasms have a critical impact on clinical management both for the carriers and their relatives.AimsWe conducted a family segregation study, in order to identify novel cancer predisposing genes in myeloid neoplasms and classify novel identified variants.Methods and ResultsWe performed a thorough genomic analysis using a large custom gene panel (256 genes), the Myelo‐Panel, targeted on cancer predisposing genes. In particular, we assessed both germline and somatic variants in four families, each with two siblings, who developed hematological neoplasms: seven acute myeloid leukemia and one Philadelphia‐positive chronic myeloid leukemia. In each family, we identified at least one novel potentially predisposing variant, affecting also genes not included in the current European LeukemiaNet guidelines for AML management. Moreover, we suggest reclassification of two germline variants as pathogenic: likely pathogenic p.S21Tfs*139 in CEPBA and VUS p.K392Afs*66 in DDX41.ConclusionWe believe that predisposition to hematological neoplasms is still underestimated and particularly difficult to diagnosed. Considering that misidentification of familiarity in myeloid neoplasms have a critical impact on the clinical management both for the carriers and their relatives, our study highlights the importance of revision, in this clinical context, of clinical practices that should include thorough reconstruction of family history and in‐depth genetic testing.

show abstract

Chediak-Higashi syndrome

Cited by 7 publications

References 71 publications

Chédiak Higashi Syndrome -A hematological Diagnosis and Review of Literature

Chédiak Higashi Syndrome -A hematological Diagnosis and Review of Literature

A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome

Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia

Contact Info

Product

Resources

About