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

Hager Jaouadi (1, 2, 3) , Lilia Kraoua (4) , Lilia Chaker (5) , Alexandre Atkinson (6) , Valérie Delague (6) , Nicolas Lévy (6, 7) , Rym Benkhalifa (8, 2) , Ridha Mrad (4) , Sonia Abdelhak (1, 2, 3) , Stéphane Zaffran (6)

1 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
2 Institut Pasteur de Tunis
3 UTM - Université de Tunis El Manar
4 Hôpital Charles Nicolle [Tunis]
5 Hôpital La Rabta [Tunis]
6 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
7 Département de génétique médicale [Hôpital de la Timone - APHM]
8 LR11IPT08 - Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules

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.

Domaines: Anatomie, Histologie, Anatomopathologie [q-bio.TO]

Hager Jaouadi, Lilia Kraoua, Lilia Chaker, Alexandre Atkinson, Valérie Delague, et al.. Novel ALPK3 mutation in a Tunisian patient with pediatric cardiomyopathy and facio-thoraco-skeletal features.. Journal of Human Genetics, 2018, 63, pp.1077--1082. ⟨10.1038/s10038-018-0492-1⟩. ⟨hal-01873754⟩