Tokiko Miyazaki

Gm ALLOTYPES IN MYASTHENIA GRAVIS

Gm typing and acetylcholine receptor antibody assay were performed on serum samples from 74 patients with myasthenia gravis (31 male, 43 female) and from 236 unrelated normal blood-donors. The haplotype Gm1,2,21 was significantly more common in patients with myasthenia gravis (relative risk = 3.24), especially those with thymoma (relative risk = 6.99). The frequency of haplotype Gm1,2,21 was further increased in patients with severe generalised myasthenia gravis (relative risk = 10.52). The frequency of Gm1,2,21 was also increased in patients with high acetylcholine receptor antibody titres (greater than 5 pmol/ml). The results indicate the presence of a pathogenic gene close to the IgG heavy-chain gene complex in the 6th chromosome in the patients with myasthenia gravis, especially those with thymoma.

A fatal case of amniotic fluid embolism with elevation of serum mast cell tryptase.

A case of a 40-year-old female who died of amniotic fluid embolism is presented. This case showed typical histological findings of this syndrome. Postmortem serum of this case showed an elevated tryptase level (67.2ng/ml, normal levels <10ng/ml). Tryptase is a neutral protease of mast cells, and an important indicator of mast cell activation and degranulation. Thus, mast cell activation, a central feature of anaphylaxis, may have been involved in the pathogenetic mechanism of this case.

IgG Heavy-Chain (GM) Allotypes and Immune Response to Insulin in Insulin-Requiring Diabetes Mellitus

IN guinea pigs1 , 2 and mice, 3 4 5 the ability to develop humoral and cell-mediated immune responses to heterologous insulins is in part controlled by immune-response genes linked to the major his...

A de novo recombination in the ABO blood group gene and evidence for the occurrence of recombination products

Abstract We have encountered a paternity case where exclusion of the putative father was only observed in the ABO blood group (mother, B; child, A1; putative father, O), among the many polymorphic markers tested, including DNA fingerprints and microsatellite markers. Cloning a part of the ABO gene, PCR-amplified from the trio’s genomes, followed by sequencing the cloned fragments, showed that one allele of the child had a hybrid nature, comprising exon 6 of the B allele and exon 7 of the O1 allele. Based on the evidence that exon 7 is crucial for the sugar-nucleotide specificity of A1 and B transferases and that the O1 allele is only specified by the 261G deletion in exon 6 of the consensus sequence of the A1 allele, we concluded that the hybrid allele encodes a transferase with A1 specificity, resulting, presumably, from de novo recombination between the B and O1 alleles of the mother during meiosis. Screening of random populations demonstrated the occurrence of four other hybrid alleles. Sequencing of intron VI from the five hybrid alleles showed that the junctions of the hybrid alleles were located within intron VI, the intron VI-exon 7 boundaries, or exon 7. Recombinational events seem to be partly involved in the genesis of sequence diversities of the ABO gene.

IgG heavy chain allotypes (Gm) in atrophic and goitrous thyroiditis.

We typed coded sera from 135 healthy controls, seventy‐six patients with autoimmne goitrous and seventy‐three with atrophic thyroiditis for IgG heavy chain markers (Gm). All subjects were Caucasian from Newfoundland. An increase in the Gm phenotype ag was found in the 149 patients with thyroiditis compared to controls (X12= 5.82, P <0.01); significance was, however, not maintained after correction for the number of variables tested. The difference in ag phenotype was more pronounced among the seventy‐three patients with atrophic thyroiditis (X12= 8.80 corrected P < 0.05). Because the haplotype ag was not significantly increased in this group, we conclude that homozygotes for Gm ag are at an increased risk of developing atrophic thyroiditis.

Sibling incest and formulation of paternity probability: case report.

Paternity determination of a fetus whose mother was admitted to an institution for the welfare and health of handicapped persons was requested of us by a doctor and lawyer of the institution. The fetus was recovered by a legal artificial abortion based on the Act on Maternity Health and Welfare (Japan) with the permission of the custodian. Commercially available MCT118, HLADQA, PM, and 9 STRs were tested for DNA samples from the fetus, the mother, her younger brother, her father, her grandfather, and 4 staff members of the institution. Only the brother was not excluded and the paternity probability was estimated at 99.857% on the basis of newly formulated expressions for multiallelic loci on the assumption of sibling incest. We concluded then that the fetus was fathered by the brother. DNA fingerprinting with multilocus and single locus minisatellite probes which were performed to confirm the paternity also support the conclusion. Bandsharing frequencies between the family members, however, did not necessarily reflect their actual kinship, which findings suggest that multilocus DNA fingerprinting requires further accumulation of data for consanguineous cases such as incest. Universal formulation for calculating paternity probability for a sibling incest case on the basis of multiallelic monolocus polymorphisms is also presented.

Mongoloid populations from the viewpoints of Gm patterns

SummaryGm systems provide unique markers for the study of human genetics, especially for the characterization of a population, the study of gene flow, and genetic drift by the presence of a unique haplotype or by marked differences in the frequencies of identical haplotypes. It has been shown that Gm haplotypes commonly present among Mongoloids are Gmag, Gmaxg, Gmab3st, and Gmafb1b3.The distribution of Gm allotypes has been investigated for the 16 Mongoloid populations from various regions in Asia, North, and South America. A striking aspect of the Gm data from the Mongoloid populations is the presence of a clear geographic cline, especially for the Gmag and Gmafb1b3 haplotypes from Southeast Asia through East Asia into South America. Moreover the Mongoloid populations were divided into two characteristic groups on the basis of the Gm patterns. A geographic cline was also found for the Gmab3st haplotype which is a marker gene of Mongoloids. Discussion was made for the reason why and how such clear geographic cline of the Gm haplotypes has been occurred in the Mongoloid populations.

Identification of a novel mutation V2321M of the cardiac ryanodine receptor gene of sudden unexplained death and a phenotypic study of the gene mutations.

Mutations of the cardiac ryanodine receptor (RyR2) gene cause catecholaminergic polymorphic ventricular tachycardia, which sometimes results in a finding of sudden unexplained death (SUD) at autopsy. We found a novel mutation (V2321M) in exon 46 of the RyR2 gene in a SUD case. V2321M was localized in a highly conservative site of the RyR2 gene, but was not found in 400 reference alleles. We previously reported two SUD cases with R420W mutations in exon 14 of the RyR2 gene. We examined possible phenotypic characteristics of all three of these cases of SUD with the RyR2 gene mutations. All cases displayed mesenteric lymph node hypertrophy as well as tendencies for aortic narrowing. By contrast, only one of the 14 SUD cases without RyR2 mutations displayed these phenotypes. This study supports the concept that postmortem genetic testing of RyR2 mutations should be considered in autopsy examinations of SUD cases. It also raises the possibility that some cases with RyR2 mutations may display phenotypic changes in lymphoid and cardiovascular organs.

Postmortem molecular screening for mutations in ryanodine receptor type 1 (RYR1) gene in psychiatric patients suspected of having died of neuroleptic malignant syndrome

Postmortem diagnosis of neuroleptic malignant syndrome (NMS) is difficult to perform, because the clinical symptoms just before death are not usually available. Malignant hyperthermia (MH) is a catastrophic, life-threatening hypermetabolic syndrome triggered by certain anesthetics. Ryanodine receptor type 1 (RYR1) gene mutations are known to be involved in susceptibility to MH. Similarities in clinical features, such as elevated body temperature, between NMS and MH have led to the suggestion that NMS is a neurogenic form of MH. In this study, we analyzed possible mutations of the RYR1 gene in 11 psychiatric patients suspected at autopsy to have died of NMS. All cases were suspected of having elevated body temperature at death, and their causes of death could not be determined by autopsy examinations. Two mutations (R4645Q and A612T) in the RYR1 gene were identified. The R4645Q mutation has previously been reported in MH patients, but five heterozygous mutations were also found in 400 Japanese control alleles. The other mutation was novel, and was not found in the same control alleles. The results of this study provide the first successful identification of RYR1 mutations in psychiatric patients suspected at autopsy of having died of NMS. However, the association between RYR1 gene mutations and cause of death in psychiatric patients suspected of dying of NMS remains unclear.

Studies on the human immunoglobulin allotypes in five populations in the USSR.

SummarySerum samples obtained from a total of 664 individuals representing five populations (Koryaks, Northern Buriats, Southern Buriats, Mongols and Uralians) in the USSR were tested for Glm(a,z,x and f) and G3m(b0,b1,b3,b4,b5,s,t,g and u), and Km(l) allotypes. According to Gm patterns, the first four of these populations are characterized by the presence of four haplotypes, namely Gm a,z;g,u, Gm a,z,x;g,u, Gm a,z;b0,b3, b5,s,t and Gm a,f;b0,b1,b3,b4,b5,u which are characteristic of Mongoloid populations, whereas the Uralian population is characterized by three haplotypes, Gm a,z;g,u, Gm a,z,x;g,u, and Gm f;b0,b1,b3,b4,b5,u which are common to Caucasoids as well as the Gm a,z;b0,b3,b5,s,t haplotype typical of northern Mongoloid populations. Results obtained from the four Mongoloid populations in Siberia indicate clear genocline, extending from Kamchatka to Mongol in which the haplotype frequency of Gm a,z;g,u changes from 0.714 to 0.431 and that of the Gm a,f;b0,b1,b3,b4,b5,u haplotype from 0.031 to 0.231. On the other hand, the Gm a,z;b0,b3,b5,s,t haplotype is found in the highest incidence (0.307) among Buriats from north Baikal, a population considered to have the most prominent Mongoloid characters, and indicates a cline from the Baikal to east and to south. In contrast to the Gm system, no significant regional differences in the frequencies of the Km1 allele were observed among these different populations.