A Novel Mutation in CACNA1S Gene Associated with Hypokalemic Periodic Paralysis Which has a Gender Difference in the Penetrance

• Published in: Journal of molecular neuroscience Vol. 46; no. 2; pp. 378 - 383
• Main Authors: Li, Fei-Feng, Li, Qian-Qian, Tan, Zhen-Xuan, Zhang, Si-Yao, Liu, Ji, Zhao, Er-ying, Yu, Gui-Chun, Zhou, Jin, Zhang, Li-Ming, Liu, Shu-Lin
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.02.2012; Springer Nature B.V
• Subjects: Adolescent; Amino Acid Sequence; Amino Acid Substitution; Asian Continental Ancestry Group - genetics; Biomedical and Life Sciences; Biomedicine; Calcium channels; Calcium Channels - chemistry; Calcium Channels - genetics; Calcium Channels - physiology; Cell Biology; Chromosomes, Human, Pair 1 - genetics; Congenital diseases; Disease; Exons - genetics; Female; Gender differences; Genes, Dominant; Genetic testing; Genomics; Genotype; Haplotypes; Hereditary diseases; Humans; Hypokalemic Periodic Paralysis - genetics; Male; Middle Aged; Models, Molecular; Molecular Sequence Data; Mutation; Mutation, Missense; Nervous system; Neurochemistry; Neurology; Neurosciences; Paralysis; Pedigree; Penetrance; Point Mutation; Potassium; Protein Conformation; Proteomics; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Sex Characteristics; Sex differences; Skeletal muscle; Species Specificity; Young Adult; China; Hypokalemic periodic paralysis; Penetrance; Mutation; CACNA1S; Gene mapping; Gender difference
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-011-9596-1

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder characterized by periodic attacks of muscle weakness associated with a decrease in the serum potassium level. Several mutations in the skeletal muscle calcium channel α-subunit gene CACNA1S have been documented to be causative for HypoPP, but mutations in other genes have also been implicated in HypoPP. To further reveal the genetic causes of HypoPP, we genotyped members of a five-generational Chinese family with HypoPP patients and identified a novel His916Gln mutation in all male HypoPP patients of the family. Clinical analysis demonstrated that the penetrance of the mutation was complete in male carriers, but we did not find evident clinical features in female carriers. This study expanded the spectrum of CACNA1S mutations associated with HypoPP and demonstrated a gender difference in the penetrance of the disease.