Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family

Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant disorder, which is characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. A major disease-causing gene for HypoPP has been identified as CACNA1S, which encodes the skeletal muscle calcium channel ?-subunit with four transmembrane domains (I-IV), each with six transmembrane segments (S1-S6). To date, all CACNA1S mutations identified in HypoPP patients are located within the voltage-sensor S4 segment. In this study we report a novel CACNA1S mutation in a new region of the protein, the S3 segment of domain III. We characterized a four-generation South American family with HypoPP. Genetic analysis identified a novel V876E mutation in all HypoPP patients in the family, but not in normal family members or 160 control people. Clinical analysis indicates that mutation V876E is associated with a severe outcome as characterized by a very early age of onset, complete penetrance and a severe prognosis including death. These results identify a new mutation in CACNA1S and expand the spectrum of CACNA1S mutations associated with HypoPP. © 2009 The Japan Society of Human Genetics All rights reserved.

• Fecha de publicación: 2009
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/22368
• Acceso en línea: https://doi.org/10.1038/jhg.2009.92; https://repository.urosario.edu.co/handle/10336/22368
• Palabra clave: Calcium channel; Genomic dna; Membrane protein; Adolescent; Adult; Alpha chain; Article; Autosomal dominant inheritance; Cacna1s gene; Child; Clinical article; Controlled study; Dna isolation; Dna sequence; Female; Gene; Gene mutation; Genetic analysis; Human; Hypokalemic periodic paralysis; Male; Muscle weakness; Potassium blood level; Preschool child; Prognosis; Protein domain; School child; Skeletal muscle; South america; Amino acid sequence; Base sequence; Calcium channels; Colombia; Dna mutational analysis; Family health; Female; Humans; Hypokalemic periodic paralysis; Male; Molecular sequence data; Mutation; Pedigree; Cacna1s; Hypokalaemic periodic paralysis; Mutation; dominant; Genes
• License: Abierto (Texto Completo)