Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report

Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling.Case Report: A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (–α3.7/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (–α3.7/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses.Conclusion: This study enlarges the mutation spectrum of β-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.

Case Report: Prenatal Genetic Counseling to Parents of Fetuses Suspected of Having Ambiguous Genitalia

The occurrence of fetuses suspected of having ambiguous genitalia will likely increase in the future. Currently, the impact of prenatal genetic counseling on parents' understanding and psychological preparedness has not been addressed. We provided prenatal genetic counseling to parents of two fetuses suspected of ambiguous genitalia. Case 1: At 22 weeks of gestation, swelling of the labia majora, and a clitoris-like structure were noted despite 46,XY detected in amniotic fluid cells. Case 2: At 28 weeks of gestation, bladder exstrophy and a scrotum-like structure were noted. At 32 weeks (Case 1) and 37 weeks (Case 2) of gestation, we shared information with parents regarding the possible difficulty of legal sex assignment at birth, and a scenario for registration of the birth certificate. At birth, both babies presented with ambiguous genitalia. For both cases, the parents remained calm on seeing their baby's genitalia for the first time. After a month, we shared medical information with parents, including karyotype, testosterone production capacity, and surgical schedule. In both cases parents assigned their respective baby's legal sex as male. Several months later, parents were questioned on prenatal genetic counseling. Case 1: Mother, “I was prepared to address our baby's genitalia calmly.” Father, “I understood the procedure of legal sex assignment.” Case 2: Mother, “Without counseling, I would have been more upset and worried.” Father, “We were assured that multidisciplinary experts would support us.” Prenatal genetic counseling provides reassurance to parents, who remain informed and emotionally secure throughout the legal sex assignment of their child.