Scholarlink

Purpose <p>Genetics of Common Variable Immunodeficiency (CVID) is complex and not fully elucidated. This study presents the clinical and genetic findings of a Danish CVID cohort and investigate whether initial genetic findings can be re-classified upon re-evaluation years later in time.</p> Methods <p>From 2016 to 2021, individuals with CVID or a CVID-like-phenotype were examined using whole exome or whole genome sequencing in combination with comprehensive gene-panels. The results were re-evaluated to ensure up-to-date American College of Medical Genetics and Genomics (ACMG) classification after a median of 3.9 years. Further, a clinical-interpretation-algorithm is proposed.</p> Results <p>Of 69 enrolled individuals, 57 met the current ESID-CVID-criteria of whom 29 (51%) had a genetic find. In total 67 ACMG class 3 to 5 variants were detected in 39 different genes. Class 3 variants (variants of uncertain significance (VUS)) accounted for 81% in the initial analysis. Upon re-evaluation 17 of 54 (31%) of the originally reported VUS were re-classified to a different ACMG-class or excluded. The developed clinical-interpretation-algorithm demonstrated high interobserver-agreement. A “definite/probable” disease causing (or contributing) genetic variant was found in 19% of the CVID-cohort and a “possible” in 18%.</p> Conclusion <p>A genetic cause of CVID could be identified in a minority of CVID-individuals, whereas the majority had no or uncertain genetic findings. Re-evaluation of genetic results over time is recommended, though VUS remain a significant challenge in CVID-genetics. Therefore, continued research in both CVID-genetics and in non-genetic causes of CVID is needed.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetics in a Danish Common Variable Immunodeficiency Cohort

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月2日

查看全文
  • Camilla Heldbjerg Drabe,
  • Mira Marie Laustsen,
  • Hanne Vibeke Marquart,
  • Hans Jakob Hartling,
  • Rasmus L. Marvig,
  • Jannik Helweg-Larsen,
  • Ann-Brit Eg Hansen,
  • Jens Lundgren,
  • Marie Helleberg,
  • Line Borgwardt,
  • Terese L. Katzenstein

摘要

Purpose

Genetics of Common Variable Immunodeficiency (CVID) is complex and not fully elucidated. This study presents the clinical and genetic findings of a Danish CVID cohort and investigate whether initial genetic findings can be re-classified upon re-evaluation years later in time.

Methods

From 2016 to 2021, individuals with CVID or a CVID-like-phenotype were examined using whole exome or whole genome sequencing in combination with comprehensive gene-panels. The results were re-evaluated to ensure up-to-date American College of Medical Genetics and Genomics (ACMG) classification after a median of 3.9 years. Further, a clinical-interpretation-algorithm is proposed.

Results

Of 69 enrolled individuals, 57 met the current ESID-CVID-criteria of whom 29 (51%) had a genetic find. In total 67 ACMG class 3 to 5 variants were detected in 39 different genes. Class 3 variants (variants of uncertain significance (VUS)) accounted for 81% in the initial analysis. Upon re-evaluation 17 of 54 (31%) of the originally reported VUS were re-classified to a different ACMG-class or excluded. The developed clinical-interpretation-algorithm demonstrated high interobserver-agreement. A “definite/probable” disease causing (or contributing) genetic variant was found in 19% of the CVID-cohort and a “possible” in 18%.

Conclusion

A genetic cause of CVID could be identified in a minority of CVID-individuals, whereas the majority had no or uncertain genetic findings. Re-evaluation of genetic results over time is recommended, though VUS remain a significant challenge in CVID-genetics. Therefore, continued research in both CVID-genetics and in non-genetic causes of CVID is needed.