Adolescent ; Calsequestrin ; genetics ; Child ; Child, Preschool ; China ; Diagnostic Errors ; Female ; Humans ; Male ; Tachycardia, Ventricular ; diagnosis

OBJECTIVETo identify mutations and variants in CASQ2 gene in 27 CPVT patients/family members.

METHODSMutational analysis was performed with direct DNA sequence analysis. The frequency of an identified CASQ2 variant was determined using the Taqman genotyping assay.

RESULTSA novel heterozygous mutation, F189L, in CASQ2 gene was identified in one family with CPVT. This mutation occurred at the evolutionarily, highly conserved phenylalanine residue at codon 189, and was not present in 1400 control individuals. No other disease-causing mutations were identified in the CASQ2 gene.

CONCLUSIONA novel mutation of F189L in the CASQ2 gene was identified.

Calsequestrin ; genetics ; DNA Mutational Analysis ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Mutation ; Pedigree ; Tachycardia, Ventricular ; genetics ; Young Adult

We characterized and compared the characteristics of Ca2+ movements through the sarcoplasmic reticulum of inferior oblique muscles in the various conditions including primary inferior oblique overaction (IOOA), secondary IOOA, and controls, so as to further understand the pathogenesis of primary IOOA. Of 15 specimens obtained through inferior oblique myectomy, six were from primary IOOA, 6 from secondary IOOA, and the remaining 3 were controls from enucleated eyes. Ryanodine binding assays were performed, and Ca2+ uptake rates, calsequestrins and SERCA levels were determined. Ryanodine bindings and sarcoplasmic reticulum Ca2+ uptake rates were significantly decreased in primary IOOA (p < 0.05). Western blot analysis conducted to quantify calsequestrins and SERCA, found no significant difference between primary IOOA, secondary IOOA, and the controls. Increased intracellular Ca2+ concentration due to reduced sarcoplasmic reticulum Ca2+ uptake may play a role in primary IOOA.
Sarcoplasmic Reticulum Calcium-Transporting ATPases ; Sarcoplasmic Reticulum/*metabolism ; Ryanodine Receptor Calcium Release Channel/metabolism ; Ryanodine/metabolism ; Oxalates/metabolism ; Oculomotor Muscles ; Ocular Motility Disorders/*metabolism/*pathology ; Muscles/*pathology ; Models, Statistical ; Middle Aged ; Male ; Humans ; Female ; Child, Preschool ; Child ; Calsequestrin/metabolism ; Calcium-Transporting ATPases/metabolism ; Calcium/metabolism/*pharmacokinetics ; Blotting, Western ; Aged ; Adult ; Adolescent