Takako Takano

Assignment of human β-galactosidase-A gene to 3p21.33 by fluorescence in situ hybridization

GM1 gangliosidosis and Morquio syndrome type B (MPS IVB) are inherited lyosomal storage disorders associated with deficiency of β-galactosidase-A (βGALA) activity. A recombinant plasmid containing a biotinylated cDNA (2.4-kb insert) encoding human β GALA was used to localize the enzyme locus by fluorescence in situ hybridization (FISH). The human β GALA gene was assigned to 3p21.33 by FISH.

Genetics of neurofibromatosis 1 in Japan-mutation rate and paternal age effect

SummaryWe have performed formal genetic studies on 26 patients (14 males, 12 females) with neurofibromatosis 1 (von Recklinghausens disease, NF1) in Japan. Family studies of 74 members of 18 kindreds revealed that 50% of the cases were caused by a new mutation; the mutation rate was assumed to be 7.3–10.5 × 10-5. A tendency of paternal age effect, which was not accounted for by the maternal age effect, was observed, but live-birth order had no significant effect. Genetic linkage of neurofibromatosis 1 to the NF1 gene or the genetic marker in the pericentric region of chromosome 17 was established in 3 informative families.

Interstitial deletion of chromosome 1q [del(1)(q24q25.3)] identified by fluorescence in situ hybridization and gene dosage analysis of apolipoprotein A-II, coagulation factor V, and antithrombin III

We report on a 12-month-old Japanese boy with an interstitial deletion of the long-arm of chromosome 1 and meningomyelocele, hydrocephalus, anal atresia, atrial septal defect, left renal agenesis, bilateral cryptorchidism, talipes equinovarus, low birth weight, growth/developmental retardation, and many minor anomalies. By conventional GTG-banding, his karyotype was first interpreted as 46,XY,del(1)(q23q24), but it was corrected as 46,XY.ish del(1)(q24q25.3) by fluorescence in situ hybridization using 11 known cosmid clones as probes. His serum levels of apolipoprotein A-II (gene symbol: APOA2, previously assigned to 1q21-q23) and coagulation factor V (F5, 1q21-q25) were normal, while serum concentration and activity of antithrombin III (AT3, 1q23-q25.1) was low. The results indicated that localization of APOA2 and F5 are proximal to the deleted region and AT3 is located within the deletion extent in the patient.

Associations of blood selenium and serum lipid levels in Japanese premenopausal and postmenopausal women

Objective: The purpose of this study was to investigate whether the level of selenium in serum or the level of selenium in erythrocytes (E-Se) was associated with serum lipid parameters (total cholesterol [TC], triglycerides, and high-density and low-density lipoprotein cholesterol [LDL-C]) in pre- and postmenopausal women. Design: Healthy female workers aged 35 to 60 years were recruited, and TC, triglycerides, high-density lipoprotein cholesterol, LDL-C, E-Se, and serum-Se levels were measured in 68 premenopausal and 59 postmenopausal women after excluding those who were treated for hyperlipidemia, receiving hormone therapy, had previous gynecological surgeries, or had irregular menstrual cycles. Information on these women, such as smoking status, current status of menstruation, and current or previous medical treatments, was obtained from a self-administered questionnaire. Correlation analyses and stepwise multiple regression analysis were applied to reveal the interrelationship between serum lipids and Se levels after adjusting for age, body mass index, smoking, and menopause status. Results: Postmenopausal women had significantly higher levels of TC, triglycerides, and LDL-C and lower levels of E-Se than premenopausal women. TC and LDL-C levels after menopause correlated negatively with E-Se. These associations were also statistically significant after controlling for age, smoking status, and body mass index. E-Se was selected as a significant related variable to explain TC and LDL-C levels as well as body mass index by multiple regression analysis. Conclusion: E-Se may be one of the possible associated factors that decrease the levels of TC and LDL-C after menopause. Further studies are needed to clarify the cause-and-effect relationship of nutritional Se status and lipid profile.

Girl with accelerated growth, hearing loss, inner ear anomalies, delayed myelination of the brain, and del(22)(q13.1q13.2).

We report on an 18-month-old Japanese girl with 46,XX,del(22)(q13.1q13.2). To our knowledge, this is the first report of a case of interstitial deletion of a 22q13.1-q13.2 segment. Clinical features included hearing loss accompanied by inner ear anomalies, hypotonia and minor anomalies, such as a long philtrum, full eyelids, epicanthus, left transverse palmar crease and psychomotor developmental delay. Despite the chromosomal deletion, her physical growth was accelerated: her height was between the 75th and 90th percentiles for her age. Her brain MRI showed signs of delayed myelination. The three-dimensional MRI of the inner ear showed abnormalities of the cochlea and vestibule in both ears. Clinical features of the patient are similar to those of a patient with a del(22)(q13.1q13.33) karyotype previously reported by Romain et al.

Variations in plasma selenium levels as a result of the menstrual cycle and pregnancy in healthy Japanese women

Plasma levels of selenium (Se) were determined consecutively during a menstrual cycle of six women in three phases (i.e., menses, follicular, and luteal). To detect possible differences in relation to normal pregnancy, plasma levels of Se were also determined in paired samples of maternal and umbilical cord blood from 12 pregnant women. No periodic changes in the plasma Se levels were observed during the menstrual cycle. The intraindividual variation, estimated by coefficients of variation, ranged from 1.9% to 9.9% among the menstrual phases of the subjects. The plasma Se level during pregnancy did not differ significantly from those of nonpregnant women, and those in the second trimester and at delivery were at similar levels (1.58±.14 and 1.48±.20 µmol/L, respectively). Compared to the levels of maternal Se at delivery, the fetal cord plasma at birth had a significant lower Se level (1.23±.34 µmol/L, p<.05).

Apolipoprotein E5 and E7 in apparently healthy Japanese males: Frequencies and relation to plasma lipid levels

SummaryIn order to determine the frequencies of apolipoproteins (apo) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common apo E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with faster migration and E5s slower migration. The gene frequencies were: the ε3 allele, 0.841; the ε4 allele, 0.095; the ε2 allele, 0.049; the ε7 allele, 0.009; the ε5 allele encoding apo E5f (the ε5f allele), 0.004; and the ε5 allele encoding apo E5s (the ε5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and apo E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that apo E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.

A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia

AbstractA tandem 24-bp insertion in the apolipoprotein E (apo E) gene was detected in a patient with elevated triglyceride, apolipoprotein (apo) CII, and apo CIII levels. This novel variant, apo E5ss, showed in position apo E5 by isoelectric focusing and was of larger molecular weight than apo E3 during two-dimensional gel electrophoresis. Polymerase chain reaction-single strand conformation polymorphism analysis using the primer pairs that cover all the coding regions was useful for rapid detection of the variant of the apo E allele. Apo E5ss may have a 24-bp insertion caused by slipped mispairing, resulting in a tandem duplication of amino acid residues 135–142 [APOE, 24-BP INS, DUP CODONS 135–142]. The proband was the only person with apo E5ss among the 806 Japanese males that we examined. We inspected six other reported apo E5 variants in the literature.

Early Menarche in Japanese Down Syndrome

To the Editor. We obtained information on 95 female patients (age 9–18 years) with Down syndrome in Japan. The period of their birth was between 1976 and 1984 (median 1980). The mean menarcheal age of 60 menstruating subjects was 12.1 ± 1.2 (SD) (Table 1). It was earlier than that of recent Japanese women (12.5 ± 1.0, N = 1,161 birth year 1974–19791) ( P < .05). View this table: Table 1. Early Menarche in Down …

11q trisomy detected by fluorescence in situ hybridization

Takano T, Yamanouchi Y, Kawashima S, Date M, Hashira S, Kida M, Abe T, Nakahori Y, Nakagome Y. 11q trisomy detected by fluorescence in situ hybridization. Clin Genet 1993: 44: 324–328.