LQTS in Northern BC: homozygosity for KCNQ1 V205M presents with a more severe cardiac phenotype but with minimal impact on auditory function.

Long QT syndrome (LQTS), a rare congenital cardiac condition associated with life-threatening ventricular arrhythmias is characterized by a prolonged QT interval on electrocardiograph corrected for heart rate [corrected QT (QTc)]. LQTS has been historically categorized into the autosomal dominant Romano-Ward syndrome (RWS) and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS). JLNS is associated with prelingual sensorineural deafness. Both types of LQTS can be caused by mutations in channel genes (e.g. KCNQ1) responsible for potassium homeostasis in cardiac myocytes and cochlea. Autosomal dominant mutations often cause the RWS phenotype and homozygous or compound heterozygous mutations contribute to JLNS. Two First Nations communities in northern British Columbia are affected disproportionately with LQTS largely due to the V205M mutation in KCNQ1, however, the pathology and phenotypic expression for those V205M homozygous has been unknown. Here, we show that four V205M homozygous individuals have a significantly higher 'peak' QTc, and a more severe cardiac phenotype compared with 41 V205M heterozygous carriers and 57 first to third degree relatives without mutations. Given the lack of prelingual deafness the homozygous V205M LQTS patients present with a phenotype more typical of RWS than JLNS.

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.

Variable onset of metachromatic leukodystrophy in a Vietnamese family.

We report two siblings with metachromatic leukodystrophy, one who presented at 7 years of age (juvenile onset) and his sister who presented at 22 years of age (adult onset). They are compound heterozygotes for two novel mutations in the arylsufatase A gene (ARSA). The responsible mutations in this Vietnamese family consist of a missense mutation with 5% enzyme activity (R143G) and a nonsense mutation (W318ter), from which no enzyme activity would be expected. These mutations in the ARSA gene have not been previously reported and may be useful when diagnosing metachromatic leukodystrophy in other affected Vietnamese individuals. The variability in presentation suggests that the genotype alone is not sufficient to determine the onset and course of the disease and modifying genetic and perhaps nongenetic factors likely contribute.