Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing.
Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features.…
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins tha…
Effects of alirocumab on types of myocardial infarction : insights from the ODYSSEY OUTCOMES trial
Gislason, Gunnar H/0000-0002-0548-402X; Malynovsky, Yaroslav V/0000-0002-9118-1104; Bhatt, Deepak L./0000-0002-1278-6245; Nikolaev, Konstantin/0000-0003-4601-6203; Sherwood, Matthew/0000-0002-4305-5883; Chumakova, Galina A/0000-0002-2810-6531; Raffel, Owen C/0000-0001-5470-7050; Leonardi, Sergio/0000-0002-4800-6132; Tse, Hung Fat/0000-0002-9578-7808; Reshetko, Olga/0000-0003-3107-7636; Pereira, Helder/0000-0001-8656-4883; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Ersanli, Murat/0000-0003-1847-3087; Muenzel, Thomas/0000-0001-5503-4150; Sandhu, Manjinder/0000-0003-2538-2079; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Manak…