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2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency
Charlyne Brakta1, Anne-Claude Tabet2, Mathilde Puel1
1Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Journal of Clinical Immunology
|November 22, 2024
Summary
CTLA4 deficiency, an inborn error of immunity, can result from 2q33 deletions. This study identified 12 patients with these deletions, revealing diverse clinical and genetic features, including contiguous gene syndromes.
Area of Science:
- Genetics
- Immunology
- Genomics
Background:
- CTLA4 deficiency is an inborn error of immunity (IEI) caused by loss-of-function variants in the CTLA4 gene.
- While point mutations are common, copy number variants (CNVs), specifically deletions encompassing CTLA4, are less understood.
- Previous reports identified large deletions in 2q33.1-2q33.2 in nine kindreds.
Purpose of the Study:
- To identify patients with 2q33 deletions encompassing CTLA4 in France.
- To investigate the clinical, immunological, and genetic characteristics of these patients.
Main Methods:
- Nationwide study in France.
- Analysis of clinical and immunological phenotypes.
- Genotyping using SNP/CGH array and high-throughput sequencing.
Main Results:
- Twelve patients from six kindreds with clinical immunodeficiency were identified.
- Five distinct heterozygous 2q33 deletions, ranging from 26 kb to 7.12 Mb, were found, affecting 1 to 41 genes.
- Neurological features were observed in three patients, including one with syndromic neurodevelopmental disorder linked to KLF7 deficiency.
Conclusions:
- 2q33 deletions encompassing CTLA4 are rare, potentially underdiagnosed in cytogenetic analysis.
- Systematic delimitation of deletions involved in IEIs is crucial for identifying contiguous gene syndromes (CGS).
- Further research is needed to fully characterize the spectrum of CGS associated with IEIs.
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