Haplotypes in the dystrophin DNA segment point to a mosaic origin of modern human diversity.

Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world.

The GM2 gangliosidoses databases: allelic variation at the HEXA, HEXB, and GM2A gene loci.

The GM2 gangliosidoses are a group of recessive disorders characterized by accumulation of GM2 ganglioside in neuronal cells. The genes responsible for these disorders are HEXA (Tay-Sachs disease and variants), HEXB (Sandhoff disease and variants), and GM2A (AB variant of GM2 gangliosidosis). We report the establishment of three relational locus-specific databases recording allelic variation at the HEXA, HEXB, and GM2A genes and accessed at the GM2 gangliosidoses home page (http://data.

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.

Formation of a ternary complex between GM2 activator protein, GM2 ganglioside and hexosaminidase A.

The GM2 activator is a 17 kDa protein required for the hydrolysis of GM2 ganglioside by the lysosomal enzyme hexosaminidase A (HexA). The activator behaves as a substrate binding protein, solubilizing GM2 ganglioside monomers from micelles (in vitro) or membranes (in vivo). However, the activator also shows a high order of specificity for activation of lysosomal hydrolases and has been predicted to form a ternary complex with the heterodimeric enzyme (alphabeta) Hex A and GM2 ganglioside.

A chronic GM2 gangliosidosis variant with a HEXA splicing defect: quantitation of HEXA mRNAs in normal and mutant fibroblasts.

Over 72 mutations have been identified in the HEXA gene of which only four (T538C, A590C, G805A, and C1495T) are believed to cause a chronic form of Tay-Sachs disease (TSD). We identified a novel HEXA mutation (IVS7, -7 G-->A) leading to chronic TSD in a Canadian patient of English ancestry. The second allele in this patient was the exon 11 4-bp insertion mutation (/1277TATC), which is the most frequent TSD allele in Ashkenazi Jews.