Mitsuyo Tanemura

Sibling risk of pervasive developmental disorder estimated by means of an epidemiologic survey in Nagoya, Japan

AbstractBroad-spectrum autism, referred to as pervasive developmental disorder (PDD), may be associated with genetic factors. We examined 241 siblings in 269 Japanese families with affected children. The sibling incidence of PDD was 10.0% whereas the prevalence of PDD in the general population in the same geographic region was 2.1%. Both of these rates are higher than those reported previously, probably because of the expanded clinical criteria applied. The prevalence in males of the general population was 3.3% and that in females was 0.82%. The sibling incidences were 7.7 and 20.0% for families in which the probands were male and female, respectively. Because the reversed sex ratios correspond to the general rule for a multifactorial threshold model, we suggest that most PDD cases result from the cumulative effects of multiple factors (mostly genetic). The sibling incidences were 0 and 10.9% for families in which the proband had low and normal birth-weight, respectively, suggesting the risk is lower in families with low-birth-weight probands.

Diagnosis of fetal rubella infection with reverse transcription and nested polymerase chain reaction : a study of 34 cases diagnosed in fetuses

OBJECTIVE Our purpose was to develop a reliable method for prenatal diagnosis of fetal rubella infection through the detection of viral ribonucleic acid extracted from the chorionic villi, amniotic fluid, or fetal blood in pregnant women. STUDY DESIGN Double amplification of rubella viral ribonucleic acid by nested polymerase chain reaction after reverse transcription was applied to samples from 34 women suspected of having rubella. The results were compared with those of serum antibody and levels of rubella virus-specific immunoglobulin M antibodies in fetal blood. RESULTS Viral ribonucleic acid was revealed in 8 of 34 cases (23.5%). In the remaining 26 cases, healthy babies were born in 24, 1 was electively aborted, and 1 died in the thirty-sixth week of pregnancy of unknown causes. CONCLUSIONS This method allowed very early detection of fetal rubella infection by sampling of chorionic villi and amniotic fluid compared with evaluation of the maternal symptoms and serum antibody levels. Fetal blood was also more useful for making a diagnosis up to the twentieth week of pregnancy than was measuring rubella virus-specific immunoglobulin M antibodies.

Is angiotensinogen gene polymorphism associated with hypertension in pregnancy

OBJECTIVE To determine whether a state of hypertension in pregnancy in the Japanese can be predicted in the early period based on detection of the M235T variant of the angiotensinogen gene, alone or with other factors. METHODS A total of 313 Japanese pregnant women were divided into 3 groups on the basis of their angiotensinogen genotype: TT, MT, and MM. Hypertension in pregnancy was diagnosed for 33 patients in all. For each group, we sought to determine what factors increased the risk of the disease. MAIN OUTCOME MEASURES The angiotensinogen M235T variant, mean arterial pressure (MAP) before the 12th gestational week, body mass index (BMI) before pregnancy, age at delivery, parity, a familial history of hypertension, and development of preeclampsia or gestational hypertension were considered. RESULTS The frequencies of the allele T were the same among preeclampsia, gestational hypertension, and normal subjects. In TT subjects, a high incidence of gestational hypertension was found for women with MAP > or = 90 mm Hg, high or low BMI before pregnancy > or = 22.0 or < 18.0, and maternal history of hypertension. In MT subjects, women who showed MAP > or = 90 mm Hg or who were above 36 years old at delivery had a high incidence of gestational hypertension. Preeclampsia could not be predicted in either group. CONCLUSIONS Hypertension in pregnancy cannot be predicted on the basis of the M235T variant of angiotensinogen gene alone. However, gestational hypertension is associated with combinations of other factors. In contrast, it is virtually impossible to predict the development of preeclampsia.

Evaluation Levels of Cytokines in Amniotic Fluid of Women with Intrauterine Infection in the Early Second Trimester

Amniotic fluid was obtained from 180 patients by amniocentesis at 16–22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.

Clinical applications of two-color telomeric fluorescence in situ hybridization for prenatal diagnosis: Identification of chromosomal translocation in five families with recurrent miscarriages or a child with multiple congenital anomalies

AbstractTwo-color fluorescence in situ hybridization (FISH) analysis using human chromosome arm-specific telomeric probes (telomeric probes) was used successfully to detect each derivative chromosome of a translocation carrier in five couples who requested a prenatal diagnosis in future pregnancies. Most of the human chromosome terminal bands are G-band-negative, and even FISH analysis using whole-chromosome painting (wcp) probes are often of insufficient complexity to detect subtle chromosomal changes. A complete set of human telomeric probes was developed to improve the sensitivity of diagnosis of microdeletions or other cryptic rearrangements in telomeric regions. Two-color telomeric FISH was the only possible method for precise prenatal diagnosis of one of the couples, because the carriers chromosomal aberration was too subtle to be detected by wcp FISH or conventional methods. We have demonstrated that two-color telomeric FISH has the potential to be a powerful new tool in the detection of cryptic chromosomal rearrangements involving telomeric regions in prenatal diagnosis precisely and in time.

Parental origin and cell stage of non‐disjunction of double trisomy in spontaneous abortion

ABSTRACT  Using polymorphic analysis of microsatellites, we investigated the parental origin and mechanism of double trisomies seen in cases of spontaneous abortion. We obtained chorionic villi from spontaneous abortions, and peripheral blood from females who experienced abortion and their spouses. Chromosomal analysis of 170 cases revealed four cases with double  trisomy.  The  karyotypes  of  these cases are 48,XX,+16,+22, 48,XXY,+18, 48,XX,+15,+21 and 48,XX,+2,+5. In the present study, the incidence of double trisomy was 2.4% of spontaneous abortions. Polymorphic analysis of microsatellites indicated that extra chromosomes were all of maternal origin in the four cases of double trisomy. The predominance of maternal origin in cases of double trisomy is similar to cases of single trisomy. The result also indicated that both extra chromosomes in two cases occurred by non‐disjunction at the first meiotic division, and extra chromosomes in the other two cases occurred by non‐disjunction at the first mitotic division. The mean maternal age in cases of double trisomy was significantly higher than that in cases of single trisomy. These findings suggest the possibility that abnormal separation of two or more chromosomes may occur simultaneously in oogonia, and that this phenomenon may increase in relation to the increase in age of women.

A retrospective evaluation of maternal serum screening for the detection of fetal aneuploidy

A retrospective evaluation of alpha‐fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) levels in maternal blood in the second trimester was conducted for cases of aneuploid pregnancies identified from a series of women who underwent amniocentesis. Blood samples were collected from 1078 women just before genetic amniocentesis was performed, mainly for individuals of advanced maternal age (greater than 35 years). Twenty‐five maternal serum samples from pregnant women with an aneuploid fetus, including 14 with Downs syndrome, were available for analysis of all three parameters. An algorithm to detect Downs syndrome was used for this analysis with a risk of ≥1:299 classified as screen‐positive, this being found for 20.4 per cent of the cases (220/1078). The actual Downs syndrome detection rate was 85.7 per cent (12/14), whereas the detection rate for all aneuploidies was 72.0 per cent (18/25). Those that were not detected were two cases of trisomy 21, one trisomy 18, two trisomy 13, three sex chromosome abnormalities, and one case of an additional marker chromosome. The data indicate that this tri‐analyte test should be provided after thorough genetic counselling and informed decision‐making regarding maternal serum screening for women who wish for a prenatal diagnosis.

Reduction of Pleural Effusion by OK-432 in a Fetus Complicated with Congenital Hydrothorax

A 29-year-old, primiparous woman was referred to our hospital at 21 weeks of gestation because of right pleural effusion in the fetus shown by routine ultrasonographic examination. Cytology revealed abundant lymphocytes, suggesting chylothorax. We removed the pleural effusion and injected OK-432 into the chest cavity at 24 and 25 weeks of gestation. Pleural effusion declined and an adhesion between the lung surface and the pleural membrane seemed to form. At 33 weeks of gestation, a female infant was born by cesarean section (1,090 g and Apgar score 6/8). Although she demonstrated slight retraction and tachypnea, management could be achieved by administration of oxygen alone without mechanical ventilation. Later, the baby was diagnosed as suffering from the Cornelia de Lange syndrome with characteristic features. OK-432 injections could thus prevent complications of chylothorax and hypoplastic lungs, without injury to either the baby or the mother.

Detection of Skin Over Cysts with Spina bifida May Be Useful Not Only for Preventing Neurological Damage during Labor but Also for Predicting Fetal Prognosis

Spina bifida is one of the most common open neural tube defects. There are two common types of spina bifida cystica, myelomeningocele and meningocele. Special attention to the thickness of the cystic sac (presence of intact skin and subcutaneous tissue) on magnetic resonance imaging is advantageous for determination of whether the child will profit from cesarean section in order to prevent neurological change (infection and drying of nerve tissue) and for management of spina bifida (most meningocele) during the perinatal period. Furthermore, skin detection may help to predict the prognosis of spina bifida after birth. Meningocele, with intact skin over the cyst, has a better clinical course than myelomeningocele. Some myelomeningoceles with neural tube defects in a lower position, also frequently having an intact skin over the cyst, have almost the same clinical course as a meningocele. From this, we hypothesize that a baby with spina bifida who has intact skin over the cyst might have a good prognosis neurologically. In this report, we concentrate attention on the skin over cysts in 3 cases (1 meningocele and 2 myelomeningoceles).

Paternal uniparental disomy of chromosome 14 and unique exchange of chromosome 7 in cases of spontaneous abortion

AbstractTo investigate the involvement of uniparental disomies (UPDs) in spontaneous abortion, the polymorphic patterns of microsatellites on each chromosome were analyzed in 164 cases of abortion. Eighty-three of the 164 cases had chromosomal abnormalities. In 79 of the remaining 81 cases with normal karyotypes, the microsatellite analysis revealed that biparental patterns were present in the informative microsatellites in all chromosomes. In one of the remaining two cases, however, the polymorphic patterns of chromosome 14 appeared to be both of paternal origin. The patterns of the distal of the long arm were homozygous, and those of the remaining region were heterozygous. That is, this fetus had paternal UPD 14, originating from meiosis I nondisjunction. In the other case, the polymorphic patterns of the distal one third of the long arm of chromosome 7 were uniparental (maternal) in origin whereas those of the remaining region of this chromosome were biparental. These findings thus suggested that this chromosome might have originated from chromatid exchange between the long arms of paternal and maternal chromosome 7 at the first mitotic division. Microsatellite analysis, however, produced no evidence of duplication or deletion of any segments. The findings also suggest the possibility that some UPDs may cause spontaneous abortion.