Clinical Report: Identification of Unique CXCR2 Compound Heterozygous Variants

Overview

This case study describes a 12-month-old boy with congenital neutropenia due to two novel CXCR2 variants. Genetic testing revealed a frameshift mutation from his mother and a missense mutation from his father, expanding the known spectrum of CXCR2-related congenital neutropenia.

Background

Congenital neutropenia is a rare inherited disorder characterized by reduced neutrophil counts, leading to increased susceptibility to infections. Recent advancements in genetic testing have identified CXCR2 loss-of-function variants as a distinct cause of this condition. Understanding the genetic basis of congenital neutropenia is crucial for accurate diagnosis and management.

Data Highlights

Key Findings

• The patient exhibited recurrent febrile respiratory infections and intermittent neutropenia.
• Whole-exome sequencing identified two novel CXCR2 variants: a frameshift mutation and a missense mutation.
• Granulocyte colony-stimulating factor (G-CSF) effectively increased ANC and WBC counts.
• Normal lymphocyte subsets and immunoglobulin levels were observed in the patient.
• This case highlights the importance of genetic testing in infants with unexplained chronic neutropenia.

Clinical Implications

The identification of CXCR2 variants in patients with congenital neutropenia can guide genetic counseling and management strategies. G-CSF therapy remains a critical component in the treatment of neutropenic episodes.

Conclusion

This case expands the understanding of CXCR2-related congenital neutropenia and underscores the role of genetic testing in diagnosis and management.

Related Resources & Content

1. Biallelic CXCR2 loss-of-function mutations define a distinct congenital neutropenia entity | Haematologica, 2021
2. European guidelines on treatment and supportive measures in chronic neutropenias: A consensus between the European Hematology Association and the EuNet‐INNOCHRON COST Action based on a systematic evidence review - PMC
3. A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia - PMC
4. The Journal of Clinical Endocrinology & Metabolism — Identification of Deep Intronic PHEX Variants in X-Linked Hypophosphatemic Rickets Using an RNA-First Method
5. Blood Cancer Journal — Developmental and Molecular Changes in Pediatric Myelodysplastic Syndrome Linked to GATA2 Deficiency Across Different Ages
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7. Brain — De Novo Monoallelic Variants in DDX17 Linked to Neurodevelopmental Disorders
8. European guidelines on treatment and supportive measures in chronic neutropenias: A consensus between the European Hematology Association and the EuNet‐INNOCHRON COST Action based on a systematic evidence review - PMC
9. A Randomized Controlled Phase III Trial of Recombinant Human Granulocyte Colony-Stimulating Factor (Filgrastim) for Treatment of Severe Chronic Neutropenia - PMC
10. Biallelic CXCR2 loss-of-function mutations define a distinct congenital neutropenia entity | Haematologica