Takefumi Bessho

Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results

Thanatophoric dysplasia (TD) is the most frequent form of neonatal lethal skeletal dysplasia. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that cause two subtypes of this disorder, type I (TDI) and type II (TDII), have been identified. This discovery has now made it possible to make a definite diagnosis of TD by molecular methods. To date, prenatal diagnosis of TD has been accomplished by ultrasonography in the second trimester. However, it is not always possible to distinguish TD fetuses in utero from the other osteochondrodysplasias by ultrasonography or radiography. We report on the prenatal diagnosis of a TD fetus, showing severe shortness of limbs and polyhydramnios, by identification of a mutation in the FGFR3 gene. Genomic DNA was isolated from the amniotic fluid and then subjected to PCR amplification. The common TDI mutation, C→T transition at nucleotide 742 in the FGFR3 gene, was identified using restriction enzyme analysis. This information was critical in obstetric management decisions later in pregnancy. However, although the mutation responsible for TDI was detected previously, we noticed some inconsistencies in the published PCR results and have proposed a correction. Copyright

Correlation between quantitative antibody titers of sperm immobilizing antibodies and pregnancy rates by treatments

Immunological infertility in women who possessed sperm immobilizing (SI) antibodies made it very difficult to conceive using the usual treatments. We examined SI antibodies by the quantitative Sperm Immobilization Test and found the antibody titers (50% sperm immobilization unit: SI50 unit) associated with pregnancy rates. Patients with high SI50 titers (greater than 10 units) did not conceive by ordinary or repeated artificial inseminations with husbands semen (AIH) except when treated with in vitro fertilization (IVF) and embryo replacement. Patients with relatively low SI50 titers (less than 10 units) could conceive either by repeated or ordinary AIH, though the success rates were lower than by IVF-embryo replacement. It is important to assess the SI50 titers by the quantitative method to select treatments for infertile women with SI antibodies. In follow-up studies of the patients who conceived successfully, it was found that SI50 titers tended to decline as pregnancy proceeded.

PRENATALLY DETECTED HEPATIC HAMARTOMA: ANOTHER CAUSE OF NON-IMMUNE HYDROPS

Although various conditions associated with non‐immune hydrops have been reported, primary hepatic tumours are rare. As a mesenchymal hamartoma of the liver is a rare benign tumour, it has not been listed as a cause of hydrops. In this report we describe a case in which a large cystic mass in the fetal liver associated with non‐immune hydrops was prenatally detected with sonography and magnetic resonance imaging, and histopathologically confirmed as a mesenchymal hamartoma of the liver.

Effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb

Background. In respirator) acidosis, it is reported that the fetal breathing movements as well as the fetal heart rate variability increase. As the increase of these two kinds of fetal activities is occasionally observed in normal conditions, it is difficult to distinguish respiratory acidosis and normal conditions by mere observation of these activities. As the third diagnostic variable, if a different feta! body movement response to respiratory acidosis is observed, it would be helpful for better diagnosis in combination with other activities. We investigated the effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb. Methods. A total of four experiments were performed on four ewes. Respiratory acidosis was induced in the fetus by maternal administration of a high carbon dioxide gas mixture for 1 hour. Fetal body movements were observed by real‐time ultrasonography. The frequency of body movements was expressed as the number of each movement in a 30‐minute period. Results. The mean pCO2 increased from 42.9 ± 4.9 mmHg to 62.9 ± 14.8 mmHg. and the mean pH decreased from 7.368 ± 0.04 to 7.209 ± 0.04 during the experiments. The frequency of fetal body movements significantly decreased. The percentage reduction of these movements of the same fetus during the experiments as compared to the control periods were as follows; the high‐frequency movements, 89.2 ± 9.7%; the rolling movements. 55.6 ± 13.5%; the simple movements. 78.3 ± 18.4%. Conclusions Normoxemic respiratory acidosis, which is reported to increase fetal breathing movements, caused a marked reduction in fetal body movements. These findings suggest that the ultrasonographic dissociation of fetal behaviors in respiratory acidosis would be potentially helpful in the diagnosis of impending fetal jeopardy.

A report on the perinatal diagnosis of 4 cases of cardiac tumors

Since 1973, we have identified 4 cardiac tumors by ultrasonography in fetal or early postnatal life. Tuberous sclerosis was diagnosed in three infants whose mother was also affected. The first infant died from acute cardiac failure after birth, and the second required cardiac surgery. The third infant had a cardiac tumor and a focal seizure at the age of 8 months. The cardiac tumor disappeared at the age of 2 years. The fourth cardiac rhabdomyoma may be the only sign of tuberous sclerosis.

Original Article: Effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb

BACKGROUND In respiratory acidosis, it is reported that the fetal breathing movements as well as the fetal heart rate variability increase. As the increase of these two kinds of fetal activities is occasionally observed in normal conditions, it is difficult to distinguish respiratory acidosis and normal conditions by mere observation of these activities. As the third diagnostic variable, if a different fetal body movement response to respiratory acidosis is observed, it would be helpful for better diagnosis in combination with other activities. We investigated the effect of respiratory acidosis on body movements in the chronically instrumented fetal lamb. METHODS A total of four experiments were performed on four ewes. Respiratory acidosis was induced in the fetus by maternal administration of a high carbon dioxide gas mixture for 1 hour. Fetal body movements were observed by real-time ultrasonography. The frequency of body movements was expressed as the number of each movement in a 30-minute period. RESULTS The mean pCO2 increased from 42.9 +/- 4.9 mmHg to 62.9 +/- 14.8 mmHg, and the mean pH decreased from 7.368 +/- 0.04 to 7.209 +/- 0.04 during the experiments. The frequency of fetal body movements significantly decreased. The percentage reduction of these movements of the same fetus during the experiments as compared to the control periods were as follows; the high-frequency movements, 89.2 +/- 9.7%; the rolling movements, 55.6 +/- 13.5%; the simple movements, 78.3 +/- 18.4%. CONCLUSIONS Normoxemic respiratory acidosis, which is reported to increase fetal breathing movements, caused a marked reduction in fetal body movements. These findings suggest that the ultrasonographic dissociation of fetal behaviors in respiratory acidosis would be potentially helpful in the diagnosis of impending fetal jeopardy.

Prenatal Diagnosis of Achondroplasia Using the Nested Polymerase Chain Reaction with Modified Primer Sets

Achondroplasia (ACH) is the most frequent form of short-limb dwarfism. Recently, the gene mutation responsible for ACH has been identified in the transmembrane domain of the fibroblast growth factor receptor 3 gene. The cause of ACH is a point mutation at nucleotide 1138 of the cDNA, resulting in the substitution of an arginine residue for a glycine. For the purpose of prenatal diagnosis of ACH, we have used the nested polymerase chain reaction to ensure the gene amplification. Although the normal allele has no restriction site around the causative sequence, we have devised an unique method to incorporate a restriction site of SplI into the normal allele only using modified primer sets. We report here the use of this polymerase chain reaction methodology which can ensure the gene amplification and omit the complicated steps of sequencing for prenatal diagnosis.