Kearns-Sayre syndrome case. Novel 5,9 kb mtDNA deletion.

BACKGROUND: Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder characterized by onset before 20 years of age and a typical clinical triad: progressive external ophthalmoplegia, pigmentary retinopathy and cardiac conduction anomalies. In most cases KSS is caused by spontaneous heteroplasmic single large-scale mitochondrial DNA (mtDNA) deletions. Long-range polymerase chain reaction (LR-PCR), next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) are the most widely applied methods for the identification of mtDNA deletions. Here, we report the case of 20-year-old male who presented with classic Kearns-Sayre syndrome, confirmed by novel 5,9 kb mtDNA deletion. METHODS AND RESULTS: LR-PCR and MLPA methods were applied to identify the mitochondrial DNA deletion for the patient, but the results were conflicting. Molecular analysis using primer walking and Sanger sequencing identified a novel 5888 base pairs mtDNA deletion (NC_012920.1:m.6069_11956del) with CAAC nucleotides repeat sequence at the breakpoints. CONCLUSION: Our study enriched the mtDNA variation spectrum associated with KSS and demonstrated the importance of choosing relevant molecular genetic methods.

CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study.

BACKGROUND: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype. METHODS: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results. RESULTS: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2 = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status. CONCLUSIONS: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.

The First Live Birth in Lithuania After Application of Preimplantation Genetic Testing.

SUMMARY BACKGROUND: Preimplantation genetic testing (PGT) is a genetic testing procedure that is performed before the implantation of embryos for the identification of genetic abnormalities. It is commonly performed when one or both expecting parents have such abnormalities and are at a high risk of passing them to their offspring. The aim of this case report is to describe the first successful IVF/ICSI/PGT procedure in Lithuania. CASE REPORT: A 27-year-old woman and a 31-year-old man, a married couple, were referred to VUHSK Santaros Fertility Center after trying to conceive for 4 years. In a previous relationship, the woman got pregnant spontaneously and decided to terminate the pregnancy. The husband does not have any children. During the medical examination, the transvaginal ultrasound revealed a low antral follicle count and low anti-Müllerian hormone level for the woman. Semen analysis for the male patient showed severe oligoastenospermia, which confirmed the previous abnormal spermogram results. Chromosome analysis revealed normal karyotype for the woman (46,XX) and Robertsonian translocation for the husband (45,XY,der(13;14)(q10;q10)). After the interdisciplinary medical team counselling, an ICSI with PGT-SR was suggested for the couple. The woman underwent controlled ovarian hyperstimulation with GnRH antagonist protocol for 11 days. Only one embryo with no unbalanced rearrangements was identified and transferred to the woman. On the 14th day post oocyte retrieval, the first serum ß-hCG result was received - 39.5 mIU/ml, and the normal gestational sac at 5 weeks and 3 days was confirmed by ultrasound examination. CONCLUSION: the first successful pregnancy was achieved in Lithuania and the first IVF/ICSI/PGT-SR newborn in Lithuania was born in 2019 - a vaginal birth of a healthy girl with gestational age of 38 weeks and 4 days and a weight of 2820 g; the Apgar score was 10/10. The IVF/ICSI/PGT procedure was successfully implemented by the multidisciplinary team in VUHSK.