Clinical application of genome-wide single nucleotide polymorphism genotyping and karyomapping for preimplantation genetic testing of Charcot–Marie–Tooth disease

Purpose@#Preimplantation genetic testing for monogenic disorders (PGT-M) has been successfully used to prevent couples with monogenic disorders from passing them on to their child. Charcot–Marie–Tooth Disease (CMT) is a genetic disorder characterized by progressive extremity muscle degeneration and loss of sensory function. For the first time in Korea, we report our experience of applying single nucleotide polymorphism genotyping and karyomapping for PGT-M of CMT disease. @*Materials and Methods@#Prior to clinical PGT-M, preclinical tests were performed using genotypes of affected families to identify informative single-nucleotide polymorphisms associated with mutant alleles. We performed five cycles of in vitro fertilization PGT-M in four couples with CMT1A, CMT2A, and CMT2S in CHA Fertility Center, Seoul Station. @*Results@#From July 2020 through August 2021, five cycles of PGT-M with karyomapping in four cases with CMT1 and CMT2 were analyzed retrospectively. A total of 17 blastocysts were biopsied and 15 embryos were successfully diagnosed (88.2%).Ten out of 15 embryos were diagnosed as unaffected (66.7%). Five cycles of PGT-M resulted in four transfer cycles, in which four embryos were transferred. Three clinical pregnancies were achieved (75%) and the prenatal diagnosis by amniocentesis for all three women confirmed PGT-M of karyomapping. One woman delivered a healthy baby uneventfully and two pregnancies are currently ongoing. @*Conclusion@#This is the first report in Korea on the application of karyomapping in PGT-M for CMT patients. This study shows that karyomapping is an efficient, reliable and accurate diagnostic method for PGT-M in various types of CMT diseases.

Identification of unbalanced complex chromosomal rearrangements in IVF-derived embryos during NGS analysis of preimplantation genetic testing: A case report

Complex chromosome rearrangements (CCRs) are structural chromosomal rearrangements involving at least three chromosomes and more than two breakpoints. CCR carriers are generally phenotypically normal but related to higher risk of recurrent miscarriage and having abnormal offspring with congenital anomalies. However, most of CCR carriers are not aware of their condition until genetic analysis of either abortus or affected baby or parental karyotyping is performed. Herein, we present the case that CCR carrier patients can be identified by preimplantation genetic testing of preimplantation embryos. An infertile male patient with severe oligoasthenoteratozoospermia was diagnosed balanced reciprocal translocation, 46,XY,t(3;11) (p26;p14) at first. After attempting the first preimplantation genetic testing for structural rearrangement (PGT-SR) cycle, we found the recurrent segmental gain or loss on 21q21.3-q22.3 of five out of nine embryos. As a result of karyotype re-analysis, the patient’s karyotype showed a balanced CCR involving chromosomes 3, 11, and 21 with three breakpoints 3p26, 11p14, and 21q21. The patient underwent two PGT-SR cycles, and a pregnancy was established after the transfer of an euploid embryo in the second cycle. Amniocentesis confirmed that the baby carried normal karyotype without mosaicism. At 37 weeks gestation, a healthy girl weighting 3,050 g was born.

A Case of Lemierre Syndrome Manifests with Persistent Fever and Neck Stiffness Following Acute Oropharyngeal Infection

Lemierre syndrome is a rare disease involving multiple organs affected by septic emboli following oropharyngeal infection. After the introduction of penicillin in the 1940s, it became a "forgotten" disease. However, due to the development of diagnostic image modalities including neck computed tomography (CT) scan, the number of published reports of Lemierre syndrome and diagnosis has been increasing since the 1990s. In this report, we describe a case of Lemierre syndrome, following oropharyngeal infection in a 16-year-old patient, who manifested with persistent fever and neck stiffness. Neck ultrasonography confirmed thrombus formation in the right internal jugular vein without definite evidence of septic emboli to other organs. After the three-week-long antibiotics therapy was completed, the thrombus in the right internal jugular vein finally disappeared.

Symptomatic Hepatitis A Virus Infection in a Newborn

Hepatitis A virus (HAV) infection is a common cause of acute hepatitis, but is rarely responsible for neonatal hepatitis. HAV infection is usually transmitted by the fecal-oral route, but during the neonatal period can be transmitted by the intrauterine vertical route or postnatal horizontal route. HAV infection is usually self-limited, but it can be potentially life-threatening in adults. The clinical course and symptoms are mild and the infection can be asymptomatic in newborns. Recently, we experienced a case of symptomatic neonatal hepatitis A. To our knowledge, this is the first case of neonatal hepatitis with HAV infection in Korea.

A Case of Gilbert's Syndrome with Severe Neonatal Hyperbilirubinemia

Gilbert's syndrome is caused by a reduction in the activity of uridine diphosphate glucuronosyltransferase (UGT) and induces chronic, non-hemolytic unconjugated hyperbilirubinemia. It has been suggested that 3-10% of the population has Gilbert's syndrome. Commonly, Gilbert's syndrome causes mild symptoms. However, a case of Gilbert's syndrome with severe neonatal hyperbilirubinemia is presented here. The patient developed jaundice three days after birth. Five days after birth, the patient's total serum bilirubin level was 34 mg/dL. The patient received intensive phototherapy and was given oral phenobarbital. Hemolytic hyperbilirubinemia was excluded on the basis of laboratory tests. Heterozygote polymorphisms of the promoter region (-3279T>G) and exon 1 (211G>A) were found in UGT1A1 gene. After discharge, the patient did not require any further treatment. This is the first case of proven Gilbert's syndrome with severe neonatal hyperbilirubinemia in Korea.

A Case of Gilbert's Syndrome with Severe Neonatal Hyperbilirubinemia

Gilbert's syndrome is caused by a reduction in the activity of uridine diphosphate glucuronosyltransferase (UGT) and induces chronic, non-hemolytic unconjugated hyperbilirubinemia. It has been suggested that 3-10% of the population has Gilbert's syndrome. Commonly, Gilbert's syndrome causes mild symptoms. However, a case of Gilbert's syndrome with severe neonatal hyperbilirubinemia is presented here. The patient developed jaundice three days after birth. Five days after birth, the patient's total serum bilirubin level was 34 mg/dL. The patient received intensive phototherapy and was given oral phenobarbital. Hemolytic hyperbilirubinemia was excluded on the basis of laboratory tests. Heterozygote polymorphisms of the promoter region (-3279T>G) and exon 1 (211G>A) were found in UGT1A1 gene. After discharge, the patient did not require any further treatment. This is the first case of proven Gilbert's syndrome with severe neonatal hyperbilirubinemia in Korea.