ABSTRACT
Deficient activity of beta-hexosaminidase A (Hex A), resulting from mutations in the HEXA gene, typically causes Tay-Sachs disease. However, healthy individuals lacking Hex A activity against synthetic substrates (i.e., individuals who are pseudodeficient) have been described. Recently, an apparently benign C739-to-T (Arg247Trp) mutation was found among individuals with Hex A levels indistinguishable from those of carriers of Tay-Sachs disease. This allele, when in compound heterozygosity with a second "disease-causing" allele, results in Hex A pseudodeficiency. We examined the HEXA gene of a healthy 42-year-old who was Hex A deficient but did not have the C739-to-T mutation. The HEXA exons were PCR amplified, and the products were analyzed for mutations by using restriction-enzyme digestion or single-strand gel electrophoresis. A G805-to-A (Gly269Ser) mutation associated with adult-onset GM2 gangliosidosis was found on one chromosome. A new mutation, C745-to-T (Arg249Trp), was identified on the second chromosome. This mutation was detected in an additional 4/63 (6%) non-Jewish and 0/218 Ashkenazi Jewish enzyme-defined carriers. Although the Arg249Trp change may result in a late-onset form of GM2 gangliosidosis, any phenotype must be very mild. This new mutation and the benign C739-to-T mutation together account for approximately 38% of non-Jewish enzyme-defined carriers. Because carriers of the C739-to-T and C745-to-T mutations cannot be differentiated from carriers of disease-causing alleles by using the classical biochemical screening approaches, DNA-based analyses for these mutations should be offered for non-Jewish enzyme-defined heterozygotes, before definitive counseling is provided.
Subject(s)
Point Mutation , beta-N-Acetylhexosaminidases/deficiency , beta-N-Acetylhexosaminidases/genetics , Adult , Amino Acid Sequence , Base Sequence , Electrophoresis, Agar Gel , Female , Gene Frequency , Genetic Carrier Screening , Genetic Testing , Hexosaminidase A , Humans , Jews , Male , Molecular Sequence Data , Mutagenesis, Site-Directed , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Pregnancy , Sequence Homology, Amino Acid , Tay-Sachs Disease/epidemiology , Tay-Sachs Disease/genetics , beta-N-Acetylhexosaminidases/chemistryABSTRACT
The aim of this study was to verify the validity and reliability of analgesia elicited by acupuncture stimulation in rabbits. Ninety-five experiments were performed using 21 adult animals. The reaction time of the avoidance response elicited by noxious heat stimulation on the snout, and the presence or absence of the start response elicited by pin-prick and clamping of the skin were studied. Bilateral electric acupuncture stimulation in the area of Tsu-san-li and Shang-chu-hsu points in the hind legs was used. The animals were either held in a soft bag, loosely attached by cords, or suspended in a hammock; the eyes were either free of blindfolded. On the basis of operational behavioral measurements, it was found that acupuncture stimulation did not produce analgesia in undisturbed, placid animals. However, during agitated or fighting periods and the immobility reflex-like state, sometimes associated with acupuncture maneuvers, long reaction times were observed. Pin-pricking and clamping stimulation of the skin were not reliable methods of noxious stimulation in the rabbit.
