Intrathoracic extramedullary haematopoiesis (EMH) is a rare entity that is usually asymptomatic. A 44 year old man with alpha-thalassaemia is described who developed dyspnoea and massive left sided haemothorax. The haemoglobin disorder was established by Hgb H staining and haemoglobin electrophoretic studies. The DNA analysis revealed it to be a case of double heterozygous terminal codon mutation with the genotype CS / T . Computed tomographic scanning and magnetic resonance imaging of the thorax showed multiple paravertebral masses which were found by thoracoscopic biopsy to be extramedullary haematopoiesis. Although no additional sclerosing pleurodesis or low dose radiation therapy was given, the lung expanded well and there has been no recurrence of haemothorax to date.

Summary α‐Thalassaemia is a common red cell disorder in Taiwan, affecting 6–8% of Taiwanese. Previous studies have shown that reactive oxygen species are generated in increased amounts in thalassaemic red cells. This implies the possible alteration of redox status in thalassaemic patients, which may adversely affect their health. In the present study, the redox status of patients with α‐thalassaemia trait and haemoglobin H (Hb H) disease was investigated. Lipid peroxidation, as measured by the level of plasma thiobarbituric acid reactive substances (TBARS), was increased in α‐thalassaemic patients, with the highest level of TBARS in Hb H disease patient. The plasma levels of vitamin A, C, and E were significantly lower in α‐thalassaemic patients than in controls. The overall antioxidant capacity in plasma was inversely correlated with the severity of α‐globin gene defect: the more severe the form of α‐thalassaemia, the lower the overall antioxidant capacity in plasma. Erythrocytes isolated from α‐thalassaemia patients had lower levels of vitamin E, glutathione, catalase and superoxide dismutase. In addition, these α‐thalassaemic red cells were more susceptible to hydrogen peroxide‐induced lipid peroxidation and decrease in deformability. All these data suggest that the α‐thalassaemic patients suffer from increased oxidative stress and antioxidant deficit, which may complicate the pathophysiology of α‐thalassaemia.

Since homozygosity of the alpha-thalassemia-1 of Southeast Asian (SEA) type deletion results in hydrops fetalis, a novel protocol based on the real-time quantitating polymerase chain reaction (PCR) technique has been developed to quantify the intact and aberrant alpha-globin genes in adults. The ratio of the normal/SEA-bearing alpha-globin genes was expressed in cycle threshold (C(T)) values. Theoretically, a relative ratio of one to one was anticipated in individuals carrying the SEA type deletion. Twenty-five heterozygous and 20 normal cases were analyzed retrospectively with this protocol. Data showed that the CT values for the intact alpha-globin gene allele and the allele bearing the SEA type deletion in carriers were 28.74+/-1.49 and 26.46+/-2.05, respectively. Therefore, the ratio of normal/SEA type deletion-bearing alpha-globin genes in the carriers was 1.09+/-0.043. No ambiguous results were observed from other less common genotypes associated with alpha-thalassemia, such as the Philippine type deletion. Based on the results, we concluded that this protocol could provide a rapid method to mass screen carriers with alpha-thalassemia-1 of SEA type deletion in this region.

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.

No abstract

The copy number variation (CNV) of 15q11.2, an emerging and common condition observed during prenatal counseling, is encompassed by four highly conserved and non-imprinted genes—TUBGCP5, CYFIP1, NIPA1, and NIPA2—which are reportedly related to developmental delays or general behavioral problems. We retrospectively analyzed 1337 samples from genetic amniocentesis for fetal CNV using microarray-based comparative genomic hybridization analysis between January 2014 and December 2019. 15q11.2 CNV showed a prevalence of 1.5% (21/1337). Separately, 0.7% was noted for 15q11.2 BP1–BP2 microdeletion and 0.8% for 15q11.2 microduplication. Compared to the normal array group, the 15q11.2 BP1–BP2 microdeletion group had more cases of neonatal intensive care unit transfer, an Apgar score of <7 at 1 min, and neonatal death. Additionally, the group was symptomatic with developmental delays and had more infantile deaths related to congenital heart disease (CHD). Our study makes a novel contribution to the literature by exploring the differences in the adverse perinatal outcomes and early life conditions between the 15q11.2 CNV and normal array groups. Parent-origin gender-based differences may help in the prognosis of the fetal phenotype; development levels should be followed up in the long term and echocardiography should be offered prenatally and postnatally for the prevention of a delayed diagnosis of CHD.

Placental mesenchymal dysplasia is an uncommon vascular anomaly of the placenta with characteristics of placentomegaly and multicystic appearance and with or without association with fetal chromosomal anomaly. We present a unique placental mesenchymal dysplasia patient with amniotic fluid karyotyping as 46, X, iso(X) (q10). Detailed molecular testing of the amniotic fluid, fetal cord blood, non-dysplastic placenta and dysplastic placenta was conducted after termination of pregnancy, from which we proved biparental/androgenetic (46, X, i(X) (q10)/45, X) mosaicism in different gestational tissues. A high portion of androgenetic cells in dysplastic placenta (74.2%) and near 100% of biparental cells in the fetus’s blood and amniotic fluid were revealed. Delicate mosaic analyses were performed, and possible pathogenesis and embryogenesis of this case were drawn up.

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.