Prevalence and phenotypes associated with ALPK3 null variants in a large French multicentric cohort: Confirming its involvement in hypertrophic cardiomyopathy.
Clin Genet
; 105(6): 676-682, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38356193
ABSTRACT
Biallelic disease-causing variants in the ALPK3 gene were first identified in children presenting with a severe cardiomyopathy. More recently, it was shown that carriers of heterozygous ALPK3 null variants are at risk of developing hypertrophic cardiomyopathy (HCM) with an adult onset. Since the number of reported ALPK3 patients is small, the mutational spectrum and clinical data are not fully described. In this multi-centric study, we described the molecular and clinical spectrum of a large cohort of ALPK3 patients. Genetic testing using targeted next generation sequencing was performed in 16 183 cardiomyopathy index cases. Thirty-six patients carried at least one null ALPK3 variant. The five paediatric patients carried two ALPK3 variants, all presented an HCM phenotype with severe outcomes (one transplantation, one heart failure and one cardiac arrest). The 31 adult patients carried heterozygous variants and the main phenotype was HCM (n = 26/31); including 15% (n = 4) presented with an apical or a concentric form of hypertrophy. Reporting a large cohort of ALPK3 patients, this collaborative work confirmed a strong association with HCM and suggesting his screening in the context of idiopathic HCM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Proteínas Quinasas
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Cardiomiopatía Hipertrófica
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Proteínas Musculares
Tipo de estudio:
Clinical_trials
/
Prevalence_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
/
Aged
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Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Clin Genet
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Dinamarca