Neutropenia in the age of genetic testing: Advances and challenges

Furutani, Elissa; Newburger, Peter E.; Shimamura, Akiko

doi:10.1002/ajh.25374

Cited by 21 publications

(19 citation statements)

References 96 publications

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“…Management of chronic neutropenia and establishment of correct diagnosis is complicated by the many possible aetiologies underlying neutropenia. Family history, patient age and blood analysis are all essential parameters to consider, and over the last decade, significant progress has been made in identifying gene mutations causing SCN 16,17 . However, there is still a considerable number of cases for which there are no known mutations and the genetic analysis require advanced technical equipment and laboratory resources.…”

Section: Discussionmentioning

confidence: 99%

“…Family history, patient age and blood analysis are all essential parameters to consider, and over the last decade, significant progress has been made in identifying gene mutations causing SCN. 16,17 However, there is still a considerable number of cases for which there are no known mutations and the genetic analysis require advanced technical equipment and laboratory resources. Previously, we have demonstrated a significant correlation between low blood plasma protein hCAP-18 levels and severity of neutropenia.…”

Section: Discussionmentioning

confidence: 99%

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The blood protein hCAP‐18 in neutropenia: An 18‐month experience of a new ELISA for clinical use

2021

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Neutropenia as an isolated clinical finding may include aetiologies ranging from severe disease to a transient condition, and differential diagnosis may be challenging. Previous data and clinical experience suggest that low levels of the neutrophil‐derived protein human 18 kDa cathelicidin antimicrobial protein (hCAP‐18) in the blood are predictive of more severe forms of neutropenia. The objective of this study was to present the results from a newly developed ELISA method that has been used in clinical routine in Sweden since 2018 for quantification of hCAP‐18 in blood plasma. Using this method, we report that patients with severe disease analysed during the study period presented with low or undetectable levels of blood plasma hCAP‐18, validating its use as screening tool for severe neutropenia. Furthermore, neutropenic patients as a group displayed lower levels of hCAP‐18 as compared to blood donors. Within the group of neutropenic patients, those with neutrophil antibodies displayed significantly higher hCAP‐18 levels compared to patients with idiopathic neutropenia. By including an analysis of hCAP‐18 in the primary investigation of neutropenia, an increased accuracy in differential diagnosis is achieved, thus contributing to reduced costs of neutropenia management.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The blood protein hCAP‐18 in neutropenia: An 18‐month experience of a new ELISA for clinical use

2021

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“…Another area that has seen rapid progress in the last decade is genetic diagnosis. The accessibility and accuracy of genetic testing in the past few years has improved drastically ( Shearer et al, 2011 ; Lin et al, 2012 ; Furutani and Shimamura, 2017 ; Men et al, 2017 ; Furutani et al, 2019 ). As genetic testing and screening improve, the ability to identify causative pathogenic alleles and potential at-risk individuals increases.…”

Section: Future Perspectivesmentioning

confidence: 99%

Gene Therapy to the Retina and the Cochlea

et al. 2021

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Vision and hearing disorders comprise the most common sensory disorders found in people. Many forms of vision and hearing loss are inherited and current treatments only provide patients with temporary or partial relief. As a result, developing genetic therapies for any of the several hundred known causative genes underlying inherited retinal and cochlear disorders has been of great interest. Recent exciting advances in gene therapy have shown promise for the clinical treatment of inherited retinal diseases, and while clinical gene therapies for cochlear disease are not yet available, research in the last several years has resulted in significant advancement in preclinical development for gene delivery to the cochlea. Furthermore, the development of somatic targeted genome editing using CRISPR/Cas9 has brought new possibilities for the treatment of dominant or gain-of-function disease. Here we discuss the current state of gene therapy for inherited diseases of the retina and cochlea with an eye toward areas that still need additional development.

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“…Clinical considerations of genetic testing are covered in recent reviews. [25][26][27] Analysis of a VUS Clinical case 1 highlights the complexity of genetic testing. Medical expertise in the disease and scientific expertise in the genes and mutations are required.…”

Section: Genetic Testingmentioning

confidence: 99%

Genetic predisposition to MDS: diagnosis and management

Furutani

Shimamura

2019

Hematology

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Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by clonal hematopoiesis with a propensity to evolve into acute myeloid leukemia. MDS presenting in children and young adults is associated with features clinically and biologically distinct from MDS arising in older adults. MDS presenting in children and young adults is associated with a higher likelihood of an underlying genetic predisposition; however, genetic predisposition is increasingly recognized in a subset of older adults. The diagnosis of a genetic predisposition to MDS informs clinical care and treatment selection. Early diagnosis allows a tailored approach to management and surveillance. Genetic testing now offers a powerful diagnostic approach but also poses new challenges and caveats. Clinical expertise in these disorders together with scientific expertise regarding the affected genes is essential for diagnosis. Understanding the basic mechanisms of genetic predisposition to myeloid malignancies may inform surveillance strategies and lead to novel therapies. The cases presented in this article illustrate challenges to the diagnosis of germline genetic predisposition to MDS and how the diagnosis affects clinical management and treatment.

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Neutropenia in the age of genetic testing: Advances and challenges

Cited by 21 publications

References 96 publications

The blood protein hCAP‐18 in neutropenia: An 18‐month experience of a new ELISA for clinical use

The blood protein hCAP‐18 in neutropenia: An 18‐month experience of a new ELISA for clinical use

Gene Therapy to the Retina and the Cochlea

Genetic predisposition to MDS: diagnosis and management

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