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Drug reactions (DR) are grouped into two basic classes. Allergic reactions through by immunological mechanisms is one of them; the second is the drug hypersensitivity reactions (DHR) that occur without the engagment of a specific immunological response. Prevelance of DHR is a extensive cause of morbidity and mortality. These severe reactions are originated from specific human leukocyte antigen (HLA) alleles. Since, HLA genes include the high rate of polymorphic loci in the genome significantly. Thus, genetic predisposition rather than the pharmacological dose effect in the etiology of DHR account for one of the most intriguing sites of pharmacogenetic research. Specific HLA associations with DHR may be varry between geographic regions and ethnic groups. Even among individuals of the same population, drug response and sensitivity may differ according as HLA alleles. Numerous investigations have provided evidence that some of HLA’s increase the risk of growing DHR. In view of the fact that the interconnection between HLA, drugs and T cell receptors in drug-responsive T cell reaction may vary widely depending on HLA alleles. According to, the allele type, the activation of the T cell and its interaction with the antigen is the most significant molecular system that causes variations in the immune response. While these features reveal the didtinctive genetic relationship of HLA alleles through DHR, there may be individuals who metabolize the drug rapidly or develop a toxic response without metabolizing it at according to HLA allele types within the pharmacokinetic effect. In this line, determining pharmacogenomic datas in societies, discovering new evidence for HLA alleles and drug sensitivity, and verifying the findings with the evidence rate will provide great benefits both in terms of health quality for drug use and cost effectiveness. Personalized pharmacological treatment with HLA identification before drug use is one of the current treatment targets in developing countries. In this review, the models that cause drug hypersensitivity reactions, the most frequently reacting drugs, the associated HLA alleles and the clinical presentations were investigated. [ABSTRACT FROM AUTHOR]

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant connective tissue disorder with multisystemic involvement caused by pathogenic genetic variations in the transforming growth factor- β pathway. Here, we report a homozygous case with LDS. A newborn male patient who had congenital diaphragmatic hernia, aortic dilatation and talipes equinovarus was referred to our medical genetics polyclinic. After clinical evaluation, next generation sequencing analysis showed a homozygous c.859C>T pathogenic missense variation [R287W (p.Arg287Trp)] in the SMAD3 gene. It was confirmed that the parents harbor the variant heterozygously. Due to the autosomal dominant inheritance pattern, rarely seen biallelic individuals are expected to have severe clinical conditions. Since there was only one previous report of an individual harboring a homozygous SMAD3 variant in the literature; this case was presented to further enhance our understanding of LDS. [ABSTRACT FROM AUTHOR]

Objective: To determine the coexistence of multiple PML-RARA transcripts in adult APL (acute promyelotic leukaemia) patients, and its impact on  the patients' laboratory parameters, treatment responses, and prognoses., Study Design: Cross-sectional study. Place and Duration of the Study: Department of Medical Genetics, Medical Faculty of Necmettin Erbakan University, Konya, Turkiye, from January 2015 to March 2023., Methodology: The study group consisted of individuals diagnosed with APL. RNA isolation was performed by taking blood or bone marrow samples and the presence of breakpoints in PML-RARA bcr1, bcr2, and bcr3 was detected using the real-time PCR. However, the quantification of PML-RARA fusion transcripts cannot be provided using the utilised kit., Results: Twelve women and eight men were examined with a mean age of 38 years (range: 19-80), and 46.5 years (range: 22-60) were examined, respectively. When evaluating patients based on isoforms, it was found that 40% had multiple isoforms. Nineteen (95%) patients achieved haematologic remission after the treatment. Only one patient who had three different isoforms did not achieve remission. The estimated median survival for patients with a single isoform and those with multiple isoforms was 78.1 months (95% CI: 37.8-117.6) and 71.7 months (46.2-97.2), respectively. Two of the patients with multiple isoforms were lost in the early stage, whereas no early-stage mortality was recorded among patients with a single isoform., Conclusion: Identifying PML-RARA isoform subtypes is important for predicting prognosis and informing clinical follow-up., Key Words: Acute promyelocytic leukaemia, Breakpoint cluster region, Isoform, PML-RARA.