Novel spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis in ethnic omani patients

2007 ◽  
Vol 82 (12) ◽  
pp. 1099-1102 ◽  
Author(s):  
Shanmugakonar Muralitharan ◽  
Yasser A. Wali ◽  
David Dennison ◽  
Zakia A. Lamki ◽  
Mathew Zachariah ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome

2021 ◽  
Vol 8 (3) ◽  
pp. e970
Author(s):  
Guillaume Taieb ◽  
Elsa Kaphan ◽  
Claire Duflos ◽  
Christine Lebrun-Frénay ◽  
Valérie Rigau ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Brain Mri ◽  
Gene Mutations ◽  
Adult Onset ◽  
Cytotoxic Lymphocyte ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Non Hodgkin Lymphoma ◽  
Treatable Condition ◽  
Perforin Expression

ObjectiveTo determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes.MethodsIn our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed.ResultsFour definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3).ConclusionsIn our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings.

scholarly journals Down-regulation of CD5 expression on activated CD8+ T cells in familial hemophagocytic lymphohistiocytosis with perforin gene mutations

2013 ◽  
Vol 74 (12) ◽  
pp. 1579-1585 ◽  
Author(s):  
Taizo Wada ◽  
Yasuhisa Sakakibara ◽  
Ryosei Nishimura ◽  
Tomoko Toma ◽  
Yasuhisa Ueno ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Down Regulation ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Pediatric CNS-isolated hemophagocytic lymphohistiocytosis

2019 ◽  
Vol 6 (3) ◽  
pp. e560 ◽  
Author(s):  
Leslie A. Benson ◽  
Hojun Li ◽  
Lauren A. Henderson ◽  
Isaac H. Solomon ◽  
Ariane Soldatos ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Chart Review ◽  
Gene Mutations ◽  
Retrospective Chart Review ◽  
Germline Mutations ◽  
Accurate Diagnosis ◽  
Hematopoietic Stem ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Disease Remission

ObjectiveTo highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL).MethodsRetrospective chart review.ResultsPatients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to any previously described neuroinflammatory etiology and have germline mutations in known FHL-associated genes with no signs of systemic inflammation. Hematopoietic stem cell transplantation (HCT) can be well tolerated and effective in achieving or maintaining disease remission in patients with CNS-FHL.ConclusionsEarly and accurate diagnosis followed by treatment with HCT can reduce morbidity and mortality in CNS-FHL, a novel, treatable syndrome.Classification of evidenceThis study provides Class IV evidence that HCT is well tolerated and effective in treating CNS-FHL.

Prenatal diagnosis of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHLH)

2002 ◽  
Vol 22 (1) ◽  
pp. 80-81 ◽  
Author(s):  
Udo zur Stadt ◽  
Michael Pruggmayer ◽  
Helena Jung ◽  
Jan-Inge Henter ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis

2001 ◽  
Vol 68 (3) ◽  
pp. 590-597 ◽  
Author(s):  
Kim Göransdotter Ericson ◽  
Bengt Fadeel ◽  
Sofie Nilsson-Ardnor ◽  
Cilla Söderhäll ◽  
AnnaCarin Samuelsson ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis

scholarly journals Late-onset cases of familial hemophagocytic lymphohistiocytosis with missenseperforin gene mutations

2007 ◽  
Vol 82 (6) ◽  
pp. 427-432 ◽  
Author(s):  
Ikuyo Ueda ◽  
Yumi Kurokawa ◽  
Kenichi Koike ◽  
Shuichi Ito ◽  
Akifumi Sakata ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Late Onset ◽  
Gene Mutations ◽  
Familial Hemophagocytic Lymphohistiocytosis

Atypical features of familial hemophagocytic lymphohistiocytosis

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4610-4612 ◽  
Author(s):  
Rosanna Busiello ◽  
Marsilio Adriani ◽  
Franco Locatelli ◽  
Mario Galgani ◽  
Giorgia Fimiani ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Late Onset ◽  
Phenotypic Expression ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Heterozygous Mutation ◽  
Disease Free Interval ◽  
Familial Hemophagocytic Lymphohistiocytosis ◽  
Asymptomatic Phase ◽  
Progressive Disorder

Abstract Familial hemophagocytic lymphohistiocytosis (FHLH) is a rare, rapidly progressive disorder of early childhood characterized by uncontrolled activation of T cells and macrophages. Although perforin gene mutations have been described in a proportion of patients with FHLH, the genotype/phenotype correlation is still limited. Only a few patients with late onset clinical manifestations have been reported. The biochemical and immunologic alterations in the asymptomatic phase are not well known. We report on a family in which 2 fraternal twins both homozygous for a perforin mutation previously described as causative of the disease, markedly differed in phenotypic expression of FHLH. The twins also had a second novel heterozygous mutation. Natural killer (NK) activity was severely impaired in the patient and was normal in the asymptomatic fraternal twin. Our report highlights that FHLH may present after a long disease-free interval during which biochemical or immunologic alterations may be not evident, thus implying a role for interfering factors. (Blood. 2004;103:4610-4612)

Sign in / Sign up

Export Citation Format

Share Document