Genetic variants in childhood-onset dilatation of thoracic aorta in a consanguineous population.

Autor: Almostafa AE; Center of Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Al-Korashy MM; Center of Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Al-Ruwaili NS; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Takroni S; Center of Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Alhabdan M; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., AlQwaee A; Prince Sultan Cardiac Center, Qassim, Saudi Arabia., Issa Z; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Khouqeer F; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Albert Brotons DC; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Almesned A; Prince Sultan Cardiac Center, Qassim, Saudi Arabia., Alhalees Z; Heart Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia., Al-Hassnan ZN; Center of Genomic Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. Electronic address: zhassnan@kfshrc.edu.sa.
Jazyk: angličtina
Zdroj: International journal of cardiology [Int J Cardiol] 2024 Nov 01, pp. 132695. Date of Electronic Publication: 2024 Nov 01.
DOI: 10.1016/j.ijcard.2024.132695
Abstrakt: Introduction: Childhood-onset thoracic aortic dilatation (TAD) is a heterogenous group of genetic conditions the inheritance of which is largely dominant. To our knowledge, the influence of consanguinity on childhood-onset TAD has not been addressed systematically. We aim to study a cohort of children with TAD in our highly consanguineous population.
Methods: Children with TAD were consecutively recruited. Based on the likelihood of a founder mutation, genetic test was categorized to either targeted gene testing or multi-gene sequencing, followed by genetic screening of first-degree relatives. Clinical data and outcome were reviewed.
Results: Thirty-three children, from 20 families, had childhood-onset TAD. Genetic test was positive in 20 children, from 13 families, providing a yield of 65 % (13/20). The median age of onset of TAD was 4.5 years. Eight variants were detected in 4 genes (FBN1, EFEMP2, ACTA2, KANSL1) with a homozygous EFEMP2 variant found in 6 families (46.2 %). Surgical intervention was required in 14 (70 %) cases (13 with EFEMP2, 1 with FBN1 variants) at a median age of 3.5 years. All patients are alive (ages range:3-31 years).
Conclusions: Our work illustrates the impact of consanguinity on the genetics of childhood-onset TAD elucidating severe presentation of recessively inherited form. Our data underscores the importance of genetic screening and early recognition of TAD to achieve excellent outcome.
Competing Interests: Declaration of competing interest No conflict of interest to disclose.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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