Hereditary ataxia and the sixth chromosome.

Possible linkage of the gene or genes for dominant hereditary ataxia and three genetic markers on the short arm of the sixth chromosome (HLA, properdin factor B [Bf], and glyoxalase I) was investigated in five families. Logarithmic odds (lod scores) were calculated for the linkages and found to be either inconclusive or in favor of nonlinkage. Caution is advised in the summing of lod scores for separate families because of the wide spectrum of clinical and anatomical manifestations of dominant hereditary ataxia. Three families with recessive hereditary ataxia were also studied. Identical haplotypes occurred in affected and unaffected siblings. It did not appear likely that the recessive genes of the parents were transmitted in linkage with the markers on the short arm of the sixth chromosome.

Studies on the change of electrophoretic mobility and the decay of catalytic activity of brain-type creatine kinase isoenzyme (CK-BB) following incubation at 37 degrees C.

Incubation of CK-BB in serum (1:3, v/v) at 37 degrees C for 3 h caused a change of its electrophoretic mobility and decay of its catalytic activity. Similar effects were observed following incubation in water. Incubation in saline somehow preserved the electrophoretic mobility but not the catalytic activity. No effect was noted when incubated at 4 degrees C for 3 h. Further study on the rate of decay revealed that the decay in albumin solution (1:50, v/v) is quite similar to that in serum. More dramatic decay was noted when incubated in water and less when incubated in saline. It was further shown that the higher the incubation temperature (4 degrees C, 25 degrees C or 37 degrees C) the faster the decay. The rate of decay of CK-MM was much slower in all conditions of incubation. Determination of isoenzyme activities by means of an immunoprecipitation method again demonstrated that CK-BB lost a great deal of its catalytic activity following incubation at 37 degrees C for 1 h, and hence falsification of the isoenzyme pattern.

[Benefits of ecogenetics in Hungary]. / Az ökogenetika magyarországi hasznosítása.

Five enzymes and one protein were studied in 10 ethnical and two reference groups involving 1370 persons. The frequency of atypical heterozygotes of plasma cholinesterase was 2.7%. Aldehyde dehydrogenase I isozyme deficiency was found in four persons including two gypsies. The low paraoxonase activity was found in 48.7% of persons examined. The proportion of gene frequencies of sigma-ALADH-1 and sigma-ALADH-2 in the locus of sigma-amino-levulinic acid dehydratase was 9:1. The percentage of slow acetylators was 56.9% in the total study sample. The rate of heterozygotes in Pi alleles of alpha 1-antitrypsin (protease-inhibitor) was 3.7% and one Pi ZZ phenotype could be observed.

Esterase-D polymorphism in Assam by cellulose acetate electrophoresis.

With the help of a simplified and quick method, cellulose acetate electrophoresis, the phenotypes of esterase D were determined in an Assamese population. The gene frequencies of Es D(1) were 0.7263 and 0.2737 for Es D(2).

delta-Aminolevulinic acid dehydrase (porphobilinogen synthase) in two families with inherited enzyme deficiency.

The inheritance of a deficient delta-aminolevulinic acid dehydrase (ALA-D; synonym: porphobilinogen synthase; EC 4.2.1.24) was studied in blood samples of two families over three generations. The propositus in each family was a young male acute hepatic porphyria patient with an almost complete ALA-D deficiency in the homozygous state (ALA-D activity less than 2% of controls). Heterozygotes are clinically non-affected (mean ALA-D 36% of controls). The mode of transmission could be traced by enzyme activity and electrophoretic polymorphism studies. Heterozygotes are detected by the demonstration of enzyme activity in the gel. The notation D was used for the gene expressing the defective enzyme. The "phenotype" D-1 was observed in six, the "phenotype" D-2 in three of all heterozygotes studied. These results are compatible with a single normal allele in heterozygotes responsible for enzyme activity. Quantitative assays and the segregation pattern in both families suggest a 3-allele-system for the inheritance of ALA-D deficiency.

Isoelectric focusing studies of human red cell PGM1 in Japanese, with special reference to the characterization of PGM17.

The distribution of phosphoglucomutase (PGM1) subtypes in human red cells was determined by isoelectric focusing in 218 Japanese samples. Nine common phenotypes were observed corresponding to the following frequencies of the four alleles at the PGM1 locus: PGM11+ 0.6560, PGM11- 0.1170, PGM12+ 0.1674 and PGM12- 0.0505. In addition, a characterization of the PGM17 allele was performed. Our results obtained in the present study revealed the possibility that the PGM17 allele may be differentiated in the two alleles of PGM17+ and PGM17- through an investigation of isoelectric focusing.

The use of serum cholinesterase in succinylcholine apnoea.

Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist.

[Succinyldicholin sensitivity resulting from genetically determined serumcholinesterase variants]. / Succinyldicholin-Empfindlichkeit als Folge genetisch bedingter Serumcholinesterasevarianten

Prolonged apnea after succinyldicholin is a pharmacogenetic phenomenon. Estimation of genetically determined cholinesterase variants of patients with a prolonged apnea after succinyldicholin or in patients with cholinesterase deficiency respectively are described. The importance of atypical cholinesterase phenotypes in anaesthesia and the possibility of a therapy of prolonged apnea are mentioned. Biochemical data of atypical cholinesterase variants as cause of the prolonged degradation of succinyldicholin as well as formal genetic aspects of cholinesterase polymorphism are discussed.

Genetic studies in Ecuador: acetylator phenotypes, red cell enzyme and serum protein polymorphisms of Shuara Indians.

Population genetic studies of Shuara Indians in Ecuador are performed for GPT, AP, PGM1, Ak, EsD, 6-PGD, Hp, Gc, C3, Bg, ChE, Tf, Pi, Bf phenotypes, IgG, IgA, IgM, C3, C3-proactivator, C4 levels and acetylator phenotypes. Some systems having a polymorphism in many other populations showed a lack of some of those alleles in the population under study (C3, ChE, Tf, AK and almost absent 6-PGD, Bg, Bf).

Monomorphism of formaldehyde dehydrogenase in different populations.

Blood samples from Koreans, Chinese, Hungarians and Germans were analyzed by isoelectric focusing on polyacrylamide gels and stained for formaldehyde dehydrogenase (FDH) activity. Three activity bands (one major and two minor) were observed in all blood samples studied. No distinct intra- and interpopulation differences were observed in the intensity of the three bands. Human autopsy liver samples also showed a similar three-activity band profile. An additional cathodic band was detected in a single case of autopsy liver extract from a Chinese subject. An apparent identity of FDH with the class III alcohol dehydrogenase was confirmed.

Polymorphism of 6-PGD in South Korea: a new genetic variant 6-PGD Korea.

During population genetic studies in Korea a new variant in the 6-phosphogluconate (6-PGD) system preliminary called 6-PGDKorea was observed.

Distribution of alpha-1-antitrypsin and haptoglobin phenotypes in bladder cancer patients.

Frequencies of the alpha 1-antitrypsin (Pi) alleles and haptoglobin phenotypes have been determined in a series of 264 North-German patients with bladder cancer. Compared to a healthy control population, we found a statistically significant decrease of Hp 2-2 phenotype in the patient series. A significant increase of the serum Pi Z allele, as previously shown for patient groups with certain other tumours, could also be confirmed for bladder cancer. Furthermore, a distinct association between a lowered M 3 allele and bladder carcinoma was observed.

Genetic markers among three population groups of Hungary.

Three ethnic groups from Hungary, the general population of Hungary, the Matyo and the Gypsies, were examined with respect to the genetic markers PGP, GLO1, GPT, ACP1, ESD, PGD, ADA, AK1, PGM1 subtypes, C3, BF, HP, GC subtypes, PI, TF subtypes and AMY2. Significant variations were noted for the gene frequencies of GPT and PGD between the Hungarian and Matyo sample. The Gypsies deviate in the systems of GLO1, ACP1, ADA, C3, BF and HP from the Hungarians.

Ecogenetic studies in Atacameño Indians.

Aldehyde dehydrogenase deficiency, N-acetyltransferase variation and the polymorphisms of alpha 1-antitrypsin, serum cholinesterase, paraoxonase, and delta-aminolevulinic acid dehydratase were investigated in 180 Atacameño Indians from the North of Chile. The genetic predisposition of these individuals for possible atypical reactions against environmental agents and drugs, as well as general implications of these findings, are discussed.

[Quantitative determination and phenotyping of ceruloplasmin in morbus Wilson (author's transl)]. / Quantitative Bestimmung und Phänotypisierung der Cäruloplasmins bei Morbus Wilson

Sera of 17 patients with Wilson's disease and of 48 relatives were investigated as to a possible correlation between ceruloplasmin phenotypes and Wilson's disease. The control group included 727 healthy subjects. The results of the quantitative determination of ceruloplasmin confirmed the overlapping in the groups of so-called heterozygotes and controls known from the literature. The ceruloplasmin phenotypes in starch gel electrophoresis we observed were of the most common phenotype Cp BB in the patients as well as in the controls. Therefore, patients with Wilson's disease also show the normal Cp-phenotypes.

Biochemical, immunological and genetic studies in leprosy. III. Genetic polymorphism of C3 and immunoglobulin profile in leprosy patients, healthy family members and controls.

148 members from 30 families (64 children) from Ethiopia, where one of more persons were affected with leprosy, were investigated for genetic polymorphism of C3, serum concentration of ss1C/ss1A-globulin and immunoglobulins A, G and M using high voltage agarose electrophoresis, immunoelectroassay and single radial immunodiffusion techniques respectively. The results are compared with related healthy controls. No association between C3 phenotypes and leprosy could be established through family studies. C3 concentration was, however, lower in leprosy patients. Difficulties and drawbacks of such studies with small families are discussed.

Studies on the polymorphism of C3, Tf and Bg in Down's syndrome and other diseases.

The distribution of phenotypes C3, Ff and Bg was investigated in sera of patients with Down's syndrome, oligophrenia, Wilson's disease and heart infarct. Quantitative determination of the concentration of C3 and C4 components of human complement was also carried out in these patients. The results are compared to healthy controls and are discussed with already reported data from other authors. Despite differences in the percentage distribution of various phenotypes in the patients' sera as compared to that of the controls, no statistically significant association could be established.

[Adrenoleukodystrophy and adrenomyeloneuropathy. Clinical biochemical and molecular genetic findings]. / Adrenoleukodystrophie und Adrenomyeloneuropathie. Klinische, biochemische und molekulargenetische Befunde.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease affecting 1 in 20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adulthood. Recently, the ALD gene has been identified by positional cloning. We report three males patients with AMN and a fourth patient with juvenile ALD. Biochemical studies showed elevated plasma concentration of saturated very-long-chain fatty acids. Genomic DNA of the patients was analysed for possible sequence variations in the ALD gene by PCR amplification and single strand conformation polymorphism analysis. Three missense mutations (Ser515Phe, Glu267Lys and Arg401Trp) and a 9-bp deletion were detected predicting, respectively, the replacement and absence of amino acids in the deduced amino acid sequence of the ALD protein. In the patients' families, detection of the respective mutations allows the identification of carriers of ALD/AMN. Mutational screening in ALD families is of practical importance in improving genetic counseling.

Distribution of apolipoprotein E genotypes in Asian Indians, Hungarians, and Papua New Guineans.

We report here the distribution of apo E genotypes and allele frequencies in Asian Indians, Hungarians, and Papua New Guineans using the DNA based analysis. Frequency of the apo E4 allele was thrice as high in Papua New Guineans as compared to the Caucasians. The rare apo E2 allele was also present in higher frequency in the Papuas as compared to other populations.

Activity of creatine kinase isoenzyme MB in serum and red cell acetylcholinesterase variants in patients with Duchenne muscular dystrophy.

Activity of creatine kinase isoenzyme MB in serum and variants of red cell acetylcholinesterase were determined in patients with Duchenne muscular dystrophy, in other forms of Dystrophy and in family members of Duchenne patients and healthy controls. Creatine kinase isoenzyme MB was observed only in all cases of DMD as well as variants of red cell acetylcholinesterase characterized by so-called inhibitor numbers. Carriers of Duchenne muscular dystrophy can be distinguished from Duchenne patients and healthy controls by estimation of Acetylcholinesterase variants.