Hepatitis B-associated nephrotic syndrome in Jamaican children.

Between December 1984 and November 1996, 171 children under 12 years old presented to the University Hospital of the West Indies with nephrotic syndrome. Hepatitis B surface antigen (HBsAg) was found in ten (6%) of these children, eight of whom had membranous nephropathy (MN), and one each had mesangial proliferative glomerulonephritis (MesN) and minimal change nephrotic syndrome (MCNS). Only those children with MesN and MCNS were steroid-sensitive. The HBsAg-positive status was identified incidentally on screening. At a mean follow-up of 34 months, seven of ten children had experienced complete or partial remission and three had persistent nephrotic syndrome, although none was in renal failure. Six of the ten had biochemical hepatitis. All the children were still HBsAg-positive. Hepatitis B virus (HBV) is a factor contributory to nephrotic syndrome in Jamaican children. As diagnostic clinical markers for HBV-associated nephropathy are usually absent, all children presenting with nephrotic syndrome should be screened for HBsAg. A policy should be implemented in Jamaica for screening pregnant women and at-risk groups for HBsAg, as well as for immunising susceptible neonates, in order to reduce the incidence of HBV-associated pathology.

Novel missense mutation in the cyclic nucleotide-binding domain of HERG causes long QT syndrome.

Autosomal-dominant long QT syndrome (LQT) is an inherited disorder, predisposing affected individuals to sudden death from tachyarrhythmias. To identify the gene(s) responsible for LQT, we identified and characterized an LQT family consisting of 48 individuals. DNA was screened with 150 microsatellite polymorphic markers encompassing approximately 70% of the genome. We found evidence for linkage of the LQT phenotype to chromosome 7(q35-36). Marker D7S636 yielded a maximum lod score of 6.93 at a recombination fraction (theta) of 0.00. Haplotype analysis further localized the LQT gene within a 6.2-cM interval. HERG encodes a potassium channel which has been mapped to this region. Single-strand conformational polymorphism analyses demonstrated aberrant bands that were unique to all affected individuals. DNA sequencing of the aberrant bands demonstrated a G to A substitution in all affected patients; this point mutation results in the substitution of a highly conserved valine residue with a methionine (V822M) in the cyclic nucleotide-binding domain of this potassium channel. The cosegregation of this distinct mutation with LQT demonstrates that HERG is the LQT gene in this pedigree. Furthermore, the location and character of this mutation suggests that the cyclic nucleotide-binding domain of the potassium channel encoded by HERG plays an important role in normal cardiac repolarization and may decrease susceptibility to ventricular tachyarrhythmias.