Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve
Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number vari...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024
|
| _version_ | 1824458632511619072 |
|---|---|
| author | DiGregorio, H Mansoorshahi, S Carlisle, SG Tovar Pensa, C Watts, A McNeely, C Sabate-Rotes, A Yetman, A Michelena, HI De Backer, JFA Mosquera, LM Bissell, MM Andreassi, MG Foffa, I Hui, DS Caffarelli, A Kim, YY Citro, R De Marco, M Tretter, JT McBride, KL Body, SC Milewicz, DM Prakash, SK |
| author_facet | DiGregorio, H Mansoorshahi, S Carlisle, SG Tovar Pensa, C Watts, A McNeely, C Sabate-Rotes, A Yetman, A Michelena, HI De Backer, JFA Mosquera, LM Bissell, MM Andreassi, MG Foffa, I Hui, DS Caffarelli, A Kim, YY Citro, R De Marco, M Tretter, JT McBride, KL Body, SC Milewicz, DM Prakash, SK |
| author_sort | DiGregorio, H |
| collection | OXFORD |
| description | Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications. Methods: Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset valve or aortic disease (EBAV) and 272 biological relatives. CNVs were detected using three independent algorithms, focusing on the 22q11.2 region (18–24 Mb). CNV burden in the EBAV cohort was compared with unselected European ancestry controls. Results: Rare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of EBAV probands. These CNVs were significantly enriched compared with the general population and segregated with BAV in families. Individuals carrying rare 22q11.2 CNVs had a higher prevalence of psychiatric diagnoses and learning difficulties, although they did not exhibit the typical features of 22q11.2DS. Importantly, these CNVs were associated with early onset or complex BAV cases, underscoring their potential clinical relevance. Conclusions: Rare 22q11.2 CNVs play a role in non-syndromic BAV, particularly in cases with early onset or complex presentations. CNV screening could be considered as part of risk stratification for patients with BAV, helping to predict complications and guide management. Trial registration number: NCT01823432. |
| first_indexed | 2025-02-19T04:28:59Z |
| format | Journal article |
| id | oxford-uuid:cb45de4d-56a7-4649-abbd-fa35a1d1c3c4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:28:59Z |
| publishDate | 2024 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:cb45de4d-56a7-4649-abbd-fa35a1d1c3c42024-12-11T20:12:16ZContribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valveJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb45de4d-56a7-4649-abbd-fa35a1d1c3c4EnglishJisc Publications RouterBMJ Publishing Group2024DiGregorio, HMansoorshahi, SCarlisle, SGTovar Pensa, CWatts, AMcNeely, CSabate-Rotes, AYetman, AMichelena, HIDe Backer, JFAMosquera, LMBissell, MMAndreassi, MGFoffa, IHui, DSCaffarelli, AKim, YYCitro, RDe Marco, MTretter, JTMcBride, KLBody, SCMilewicz, DMPrakash, SKBackground: Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications. Methods: Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset valve or aortic disease (EBAV) and 272 biological relatives. CNVs were detected using three independent algorithms, focusing on the 22q11.2 region (18–24 Mb). CNV burden in the EBAV cohort was compared with unselected European ancestry controls. Results: Rare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of EBAV probands. These CNVs were significantly enriched compared with the general population and segregated with BAV in families. Individuals carrying rare 22q11.2 CNVs had a higher prevalence of psychiatric diagnoses and learning difficulties, although they did not exhibit the typical features of 22q11.2DS. Importantly, these CNVs were associated with early onset or complex BAV cases, underscoring their potential clinical relevance. Conclusions: Rare 22q11.2 CNVs play a role in non-syndromic BAV, particularly in cases with early onset or complex presentations. CNV screening could be considered as part of risk stratification for patients with BAV, helping to predict complications and guide management. Trial registration number: NCT01823432. |
| spellingShingle | DiGregorio, H Mansoorshahi, S Carlisle, SG Tovar Pensa, C Watts, A McNeely, C Sabate-Rotes, A Yetman, A Michelena, HI De Backer, JFA Mosquera, LM Bissell, MM Andreassi, MG Foffa, I Hui, DS Caffarelli, A Kim, YY Citro, R De Marco, M Tretter, JT McBride, KL Body, SC Milewicz, DM Prakash, SK Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title | Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title_full | Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title_fullStr | Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title_full_unstemmed | Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title_short | Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve |
| title_sort | contribution of rare chromosome 22q11 2 copy number variants to non syndromic bicuspid aortic valve |
| work_keys_str_mv | AT digregorioh contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT mansoorshahis contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT carlislesg contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT tovarpensac contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT wattsa contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT mcneelyc contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT sabaterotesa contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT yetmana contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT michelenahi contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT debackerjfa contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT mosqueralm contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT bissellmm contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT andreassimg contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT foffai contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT huids contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT caffarellia contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT kimyy contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT citror contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT demarcom contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT tretterjt contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT mcbridekl contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT bodysc contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT milewiczdm contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve AT prakashsk contributionofrarechromosome22q112copynumbervariantstononsyndromicbicuspidaorticvalve |