Ítem
Acceso Abierto
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a South American family
Título de la revista
Autores
Ke, Tie
Gomez, Cladelis Rubio
Mateus, Heidi Eliana
Castano, Juan Andres
Wang, Qing Kenneth
Archivos
Fecha
2009
Directores
ISSN de la revista
Título del volumen
Editor
Buscar en:
Métricas alternativas
Resumen
Abstract
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.
Palabras clave
Keywords
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 , Genes , Humans , Hypokalemic periodic paralysis , Male , Molecular sequence data , Mutation , Pedigree , Cacna1s , Hypokalaemic periodic paralysis , Mutation
