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Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of ⩾50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies. [ABSTRACT FROM AUTHOR]

To construct a polymerase chain reaction (PCR) site-directed mutagenesis of the long QT syndrome KCNQ1 gene in vitro, two sets of primers were designed according to the sequence of KCNQ1 cDNA and a mismatch was introduced into primers. Mutagenesis was performed in a two-step PCR. The amplified fragments from the third PCR which contained the mutation site were sub-cloned into the T-vector pCR2.1. Then, the fragments containing the mutation site was obtained from pCR2.1 using restriction enzymes digestion and inserted into the same restriction site of pIRES2-EGFP-KCNQ1. The sequencing analysis shows that the mutation site was correct. Mutation from A to G in site 983 of KCNQ1 cDNA was found. Using the Effectene transfection reagent, pIRES2-EGFP-KCNQ1 (G983A) was transfected into HEK cells successfully. These results may shed light on further functional study of KCNQ1 gene. [ABSTRACT FROM AUTHOR]

Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies, which cause syncope and sudden death. Inherited LQTS is represented by the autosomal dominant Romano-ward syndrome (RWS), which is not accompanied by congenital deafness, and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), which is accompanied by congenital deafness. The LQTS-causing mutations have been reported in patients and families from Europe, North America and Japan. Few genetic studies have been carried out in families with JLNS from China. This study investigates the molecular pathology in four families with LQTS (including a family with JLNS) in the Chinese population. Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A mutation. A missense mutation G314S in an RWS family was identified, and a single nucleotide polymorphism (SNP) G643S was indentified in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients. Our data provide useful information for the identification of polymorphisms and mutations related to LQTS and the Brugada Syndrome (BS) in Chinese populations. [ABSTRACT FROM AUTHOR]

Hypokalemic 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. The skeletal muscle calcium channel a-subunit geneCACNA1Sis a major disease-causing gene for HypoPP, however, only three specific HypoPP-causing mutations, Arg528His, Arg1,239His and Arg1,239Gly, have been identified inCACNA1Sto date. In this study, we studied a four-generation Chinese family with HypoPP with 43 living members and 19 affected individuals. Linkage analysis showed that the causative mutation in the family is linked to theCACNA1Sgene with a LOD score of 6.7. DNA sequence analysis revealed a heterozygous C to G transition at nucleotide 1,582, resulting in a novel 1,582C?G (Arg528Gly) mutation. The Arg528Gly mutation co-segregated with all affected individuals in the family, and was not present in 200 matched normal controls. The penetrance of the Arg528Gly mutation was complete in male mutation carriers, however, a reduced penetrance of 83% (10/12) was observed in female carriers. No differences were detected for age-at-onset and severity of the disease (frequency of symptomatic attacks per year) between male and female patients. Oral intake of KCl is effective in blocking the symptomatic attacks. This study identifies a novel Arg528Gly mutation in theCACNA1Sgene that causes HypoPP in a Chinese family, expands the spectrum of mutations causing HypoPP, and demonstrates a gender difference in the penetrance of the disease. [ABSTRACT FROM AUTHOR]