Reproductive History of a Woman With 8p and 18p Genetic Imbalance and Minor Phenotypic Abnormalities

Abstract

We report on the phenotype and the reproductive history of an adult female patient with an unbalanced karyotype: 8p23 and 18p11.3 terminal deletions and 8p22 duplication. The indication for karyotyping of the 28-year-old patient was a structural rearrangement in her miscarriage specimen: 45,ХХ,der(8;18)t(8;18)(p23;p11.3). Unexpectedly, the patient had the same karyotype with only one normal chromosome 8, one normal chromosome 18, and a derivative chromosome, which was a product of chromosomes 8 and 18 fusion with loss of their short arm terminal regions. Fluorescence in situ hybridization revealed that derivative chromosome was a pseudodicentric with an active centromere of chromosome 8. Array comparative genomic hybridization confirmed 8p and 18p terminal deletions and additionally revealed 8p22 duplication with a total of 43 OMIM annotated genes being affected by the rearrangement. The patient had minor facial and cranial dysmorphia and no pronounced physical or mental abnormalities. She was socially normal, had higher education and had been married since the age of 26 years. Considering genetic counseling, the patient had decided to conceive the next pregnancy through in vitro fertilization (IVF) with preimplantation genetic testing for structural chromosomal aberrations (PGT-SR). She underwent four IVF/PGT-SR cycles with a total of 25 oocytes obtained and a total of 10 embryos analyzed. Only one embryo was balanced regarding chromosomes 8 and 18, while the others were unbalanced and demonstrated different combinations of the normal chromosomes 8 and 18 and the derivative chromosome. The balanced embryo was transferred, but the pregnancy was not registered. After four unsuccessful IVF/PGT-SR cycles, the patient conceived naturally. Non-invasive prenatal testing showed additional chromosome 18. The prenatal cytogenetic analysis of chorionic villi revealed an abnormal karyotype: 46,ХХ,der(8;18)t(8;18)(p23;p11.3)mat,+18. The pregnancy was terminated for medical reasons. The patient has a strong intention to conceive a karyotypically normal fetus. However, genetic counseling regarding this issue is highly challenging. Taking into account a very low chance of balanced gametes, emotional stress caused by numerous unsuccessful attempts to conceive a balanced embryo and increasing age of the patient, an IVF cycle with a donor oocyte should probably be considered.

Age and Serum AMH and FSH Levels as Predictors of the Number of Oocytes Retrieved from Chromosomal Translocation Carriers after Controlled Ovarian Hyperstimulation: Applicability and Limitations

“…Prior to the start of an IVF/PGT-SR cycle, cytogenetic diagnoses in all of the translocation carriers were verified by conventional karyotyping followed by fluorescence in situ hybridization (FISH) if required. All conventional karyotyping and FISH procedures including PHA-stimulation of peripheral blood lymphocytes, preparation of metaphase chromosomes, QFH/AcD staining and hybridization were performed according to standard protocols with modifications repeatedly used in our previous studies [ 6 , 7 , 8 , 9 , 10 ]. The final cytogenetic diagnoses are summarized in Table A1 .…”

Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults

“…We assembled these laboratory traits using a MySQL database and applied QC using R. We retained only individuals with available genotype data, and traits that were normally distributed and met the criterion of phenotype missing rate < 80%. Frequency distributions of traits were inspected using hist_plot.R that facilitates manual inspection of continuous traits by providing fast, high-throughput visualization along with necessary summary statistics of each visualized traits [61]. hist_plot.R is part of the CLARITE [61], which is available at https://github.com/HallLab/ clarite.…”

“…Frequency distributions of traits were inspected using hist_plot.R that facilitates manual inspection of continuous traits by providing fast, high-throughput visualization along with necessary summary statistics of each visualized traits [61]. hist_plot.R is part of the CLARITE [61], which is available at https://github.com/HallLab/ clarite. We also cross-referenced the retained traits to other published work that analyzed the same traits using these clinical trials datasets [25,26].…”

Hybrid sequencing resolves two germline ultra-complex chromosomal rearrangements consisting of 137 breakpoint junctions in a single carrier

“…In contrast to BFB cycles, chromothripsis is a single event of localized scattering of one or a few (< 4) chromosomes; once scattered, the fragments are rapidly joined in a seemingly random fashion (Pellestor 2019 ). Chromothripsis may involve deletions and copy number neutral fragments (Korbel and Campbell 2013 ) and may be initiated through numerous events, including the formation of micronuclei, viral insertion, or radiation (Koltsova et al 2019 ). Chromothripsis has been observed in cancer (Cortés-Ciriano et al 2020 ) as well as in germline (Macera et al 2015 ).…”

“…As such, there is a great value in characterizing CCRs, the molecular characterization of CCRs may provide insights on genetic repair mechanisms and double-stranded breakage (Koltsova et al 2019 ), as well as provide details on the structure and function of the genome in general (Pellestor 2019 ).…”