1/3. A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (tay-sachs disease) patients.Samples of genomic dna from three unrelated American black infants having both biochemical and clinical features of classical infantile tay-sachs disease were sequenced following PCR amplification. A G T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration.- - - - - - - - - - ranking = 1keywords = black (Clic here for more details about this article) |
2/3. Ultrastructural pathology of skin biopsy and fibroblast enzyme studies in a case of GM2-gangliosidosis with deficient hexosaminidase a and thermolabile hexosaminidase b.A 2 year-old non-Jewish boy had muscle hypertonia, a black cherry spot, dementia, and seizures. His skin biopsy showed membranous cytoplasmic bodies in axonal terminals and zebra body-like inclusions in schwann cells. Biochemically, a deficiency of Hex A and two separate Hex B peaks indicated a type 1 (B variant, Tay Sachs) like subvariant of GM2-gangliosidosis.- - - - - - - - - - ranking = 0.090909090909091keywords = black (Clic here for more details about this article) |
3/3. Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical tay-sachs disease (type B GM2 gangliosidosis).Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. cerebrospinal fluid analyses revealed vacuolated macrophages that contained long parallel needle-like intracytoplasmic inclusions. light microscopically, nerve cell bodies throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had pale granular to finely vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with sudan black and Luxolfast blue stains. Within the brain there were occasional axonal spheroids, foci of astrogliosis and scattered microglial cells with abundant pale foamy cytoplasm. Electron microscopy of the brain and retina revealed numerous neurons and ganglion cells, respectively, with multiple membrane-bound structures that contained compact electron-dense membranous whorls and fewer parallel membranous stacks. Thin layer chromatography of total lipid extracts of the cerebral cortex of both cases revealed massive accumulation of G(M2) ganglioside. Crude kidney extracts of the two affected deer were able to hydrolyze 4-methylumbelliferyl beta-GlcNAc, but not 4-methylumbelliferyl beta-GlcNAc-6-sulfate, indicating the defect of beta-hexosaminidase a. Cellogel electrophoresis of the kidney extracts also revealed the deficiency of beta-hexosaminidase a in the two deer. It is concluded that these two deer had the biochemical lesion identical to that of human type B G(M2) gangliosidosis (classical tay-sachs disease).- - - - - - - - - - ranking = 0.090909090909091keywords = black (Clic here for more details about this article) |