Novel ALPK3 mutation in a Tunisian patient with pediatric cardiomyopathy and facio-thoraco-skeletal features

• Published in: Journal of human genetics Vol. 63; no. 10; pp. 1077 - 1082
• Main Authors: Jaouadi, Hager, Kraoua, Lilia, Chaker, Lilia, Atkinson, Alexandre, Delague, Valérie, Levy, Nicolas, Benkhalifa, Rym, Mrad, Ridha, Abdelhak, Sonia, Zaffran, Stéphane
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2018
• Subjects: Adult; Cardiomyopathy; Cardiomyopathy, Dilated - diagnostic imaging; Cardiomyopathy, Dilated - genetics; Child, Preschool; Cleft lip/palate; Dilated cardiomyopathy; Female; Homozygote; Human health and pathology; Humans; Life Sciences; Male; Muscle Proteins - genetics; Mutation; Patients; Pediatrics; Protein Kinases - genetics; Tissues and Organs; Tunisia
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-018-0492-1

Pediatric cardiomyopathy is a complex disease with clinical and genetic heterogeneity. Recently, the ALPK3 gene was described as a new hereditary cardiomyopathy gene underlying pediatric cardiomyopathies. Only eight patients carrying mutations in ALPK3 have been reported to date. Here, we report a 3-year-old male patient with both hypertrophic and dilated cardiomyopathy. The patient presented dysmorphic features and skeletal deformities of hands and feet, pectus excavatum, and cleft palate. The genetic investigation was performed by whole-exome sequencing in the patient and his parents. We identified a novel homozygous mutation in ALPK3 (c.1531_1532delAA; p.Lys511Argfs*12). Our work extends the phenotypic spectrum of the ALPK3-associated cardiomyopathy by reporting additional clinical features. This is the first study of a Tunisian patient with mutation in the ALPK3 gene. In conclusion, ALPK3 should be included in the list of genes to be considered in genetic studies for patients affected with pediatric syndromic cardiomyopathy.