AI Article Synopsis
Article Abstract
Jagunal homolog 1 (JAGN1) has been recognized as an essential protein in neutrophil function. The mutated JAGN1 is responsible for immunodeficiency related to innate and humoral defense mechanisms. This deficiency impairs neutrophil development and function, leading to recurrent infections and facial dysmorphism as phenotypic consequences of severe congenital neutropenia (SCN). We report two siblings having the reported JAGN1 mutation with different clinical manifestations. Recurrent abscess formation unresponsive to antibiotic therapy, a history of delayed umbilical separation, frequent bacterial or fungal infection, dysmorphic face, failure to thrive, and other coexisting organ abnormalities should prompt physicians to syndromic immunodeficiencies involving neutrophils. Genetic investigations to elucidate the responsible mutation is critical as clinical management varies. Once the diagnosis is confirmed, a multi-disciplinary team should perform further workups to investigate other coexisting malformations and neurodevelopmental evaluation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148515 | PMC |
| http://dx.doi.org/10.1186/s12887-023-04024-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Case report: Granulocyte-macrophage colony-stimulating factor sargramostim did not rescue the neutrophil phenotype in two patients with JAGN1-mutant severe congenital neutropenia.
Front Immunol
September 2024
Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Article Synopsis
- Patients with JAGN1 mutations experience severe congenital neutropenia, leading to high rates of bacterial infections and poor response to G-CSF therapy.
- Two unrelated patients, one pregnant and one an infant, received GM-CSF after G-CSF failure, but neither showed an increase in neutrophil counts and treatment was eventually stopped due to further declines and infections.
- Despite the promising results in a mouse model, GM-CSF therapy did not benefit the patients, highlighting the need for early evaluation for hematopoietic stem cell transplantation in these cases.
A JAGN1-associated severe congenital neutropenia zebrafish model revealed an altered G-CSFR signaling and UPR activation.
Blood Adv
August 2024
Department of Oncology, Hematology, Clinical Immunology, and Rheumatology, University Hospital Tuebingen, Tuebingen, Germany.
A variety of autosomal recessive mutations in the JAGN1 gene cause severe congenital neutropenia (CN). However, the underlying pathomechanism remains poorly understood, mainly because of the limited availability of primary hematopoietic stem cells from JAGN1-CN patients and the absence of animal models. In this study, we aimed to address these limitations by establishing a zebrafish model of JAGN1-CN.
View Article and Find Full Text PDFGenetic backgrounds and clinical characteristics of congenital neutropenias in Israel.
Eur J Haematol
August 2024
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Article Synopsis
- Congenital neutropenias in Israel show a diverse genetic landscape, with a focus on severe cases, particularly highlighting the prevalence of G6PC3 variants in consanguineous populations.
- A total of 65 patients were analyzed, revealing that the majority of severe cases were linked to ELANE and G6PC3 mutations, while some had other genetic variants or conditions like cyclic neutropenia or Shwachman-Diamond syndrome.
- The study emphasizes the importance of ongoing monitoring for patients due to a significant occurrence of myeloid transformation, indicating gaps in medical understanding as some patients remain without a clear genetic diagnosis.
Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses.
J Clin Pathol
August 2024
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA
The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia.
View Article and Find Full Text PDFSevere congenital neutropenia due to jagunal homolog 1 () mutation: a case report and literature review.
Front Pediatr
July 2023
Harvard Medical School, Boston, MA, United States.
Severe congenital neutropenia caused by jagunal homolog 1 () mutation is a rare condition resulting from maturation arrest secondary to endoplasmic reticulum stress response from impaired neutrophil protein glycosylation. Here, we report a case of a 4-year-old boy who presented with a history of recurrent infections and manifestations, including recurrent intracranial hemorrhage. A review of similar cases reported in the literature indicates that a bleeding diathesis has not been previously described in these patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!