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Abstract Background Long QT syndrome (LQTS) is a cardiac disorder characterized by prolonged QT intervals on electrocardiograms (ECG), ventricular arrhythmias, and sudden death. Clinically, two inherited forms of LQTS have been defined: autosomal dominant LQTS or Romano-Ward syndrome (RWS) not associated with deafness and autosomal recessive LQTS or Jervell and Lange-Nielsen syndrome (JLNS) associated with deafness. Methods A Chinese family with both RWS and JLNS was identified. Family members were diagnosed based on the presence of a prolonged QT interval as seen on a 12-lead ECG and a medical history of syncope, palpitation, and deafness. Mutational studies in the KCNQ1 potassium channel gene were performed using direct DNA sequence analysis and restriction length polymorphism analysis. Results The proband in the Chinese family and her brother had previously been diagnosed with JLNS, and two other members were affected with RWS. The proband was also affected with atrial fibrillation. A single nucleotide substitution of C to T at nucleotide 965 of KCNQ1 was identified, and the mutation resulted in the substitution of a threonine residue at codon 322 by a methionine residue (T322M). The novel heterozygous T322M mutation was identified in two patients with RWS, one member with borderline QTc, and two normal family members. The two JLNS patients in the family carried the homozygous T322M mutation. The T322M mutation was not found in 200 Chinese normal controls. Conclusion Our results suggest that T322M is a novel mutation that caused RWS with high intrafamilial variability in the heterozygous carriers and typical JLNS in the homozygous carriers within this Chinese family. The T322M mutation is the first mutation identified for JLNS in the Chinese population.

Abstract: Objective: To study the gene mutations of homeobox transcription factor(CSX/NKX2.5) associated with a Chinese family with secundum atrial septal defect(ASD). Methods: Polymerase chain reaction and DNA sequencing were used to check all the members in the family with ASD, and single strand conformation polymorphism analysis(SSCP) was used to check 126 normal control people for detecting the mutations of CSX/NKX2.5 gene. Results: Three mutations, G270A(Glu32Lys), G378A(Glu68Lys)andG390A(Glu72Lys) were identified in CSX/NKX2.5 gene of ASD patients. However, the other members in the family with ASD and the control did not have such gene mutations. Conclusion: These mutations of CSX/NKX2.5 gene, which were identified in a Chinese family, may be one of the secundum ASD etiologic causes. [Copyright &y& Elsevier]

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]

Purpose: A four-generation Chinese family with 13 members affected with autosomal dominant congenital posterior polar cataract was studied. The purpose of this study was to identify the disease-causing gene in the family and to validate that mutations in CRYAB, the alphaB-crystallin gene, cause the congenital cataract., Methods: Linkage analysis was performed with a panel of microsatellite markers flanking candidate genetic loci for cataracts, including 14 known autosomal dominant congenital cataract (ADCC) genes. For mutation analysis, the complete coding region and exon-intron boundaries of CRYAB were sequenced with DNA from the proband. Single-strand conformation polymorphism (SSCP) analysis for exon 1 of CRYAB was performed in all family members and 200 normal control subjects., Results: The disease gene in the Chinese family was mapped to chromosome 11 in region q22-22.3 with a maximum lod score of 4.52. Direct DNA sequence of CRYAB revealed a heterozygous C-->T transition at nucleotide 58, resulting in a novel 58 C-->T (Pro20Ser) mutation. The Pro20Ser mutation cosegregated with all affected individuals and was not present in unaffected members in the family or in 200 normal control subjects. The mutation occurs at the evolutionarily conserved residue Pro20 in the N-terminal region of alphaB-crystallin., Conclusions: To date, only one CRYAB mutation has been associated with congenital isolated cataract. This study identified a second novel mutation in CRYAB in a large Chinese cataract family. Together, these results provide strong evidence that CRYAB is a pathogenic gene for congenital cataract.