Global Medical Genetics最新文献

Spinal muscular atrophy (SMA) is a rare, recessively inherited neurodegenerative disorder caused by the presence of pathogenic variants in the SMN gene. As it is the leading inherited cause of infant mortality, identification of SMN gene pathogenic variant carriers is important for diagnostic purposes with effective genetic counseling. Multiple ligation probe analysis (MLPA), a probe-based method, is considered as the gold standard for SMA carrier analysis. However, MLPA might give false-negative results in cases with variations in the probe-binding regions. Here, we present a case born to consanguineous SMA carrier parents. Prenatal diagnosis with MLPA failed to detect the compound heterozygous mutant state of the proband and she was born unfortunately with SMA phenotype. Further analysis with a real-time polymerase chain reaction kit was able to detect the compound heterozygous state of the patient and was confirmed with targeted next-generation sequencing technology.

Hepatitis C virus (HCV) is a causative agent that causes chronic liver diseases worldwide. It is a little, enclosed, single-stranded ribonucleic acid (RNA) virus. The recognition of the pathogenic HCV genotype is critical for the remedy of its sufferers. The aim of this study was to identify the HCV RNA genotype to decide the correct treatment of hepatitis C positive sufferers in Bangladesh. Blood samples were collected from 390 individuals and isolated RNA (60 µg) from blood plasma. Extracted RNA was used for quantitative HCV RNA, and complementary DNA (cDNA) was prepared by polymerase chain reaction (PCR) conducted by reverse transcriptase enzyme. This cDNA amplified in multiplex by RT-PCR, which was performed with specific set of primers. The HCV RNA genotype was detected 297 of 390 patients. Of the 390 test samples, 200 (51.28%) samples were from males and 190 (48.71%) were from females, with age ranging from 5 to 78 years. In all, 166 of 200 male samples and 131/190 female samples were found positive for HCV. Of these 390 participants included in the study, 213 (54.61%) were identified as genotype 3 positive, 78 (20%) as genotype 1 positive, 6 (1.53%) as genotype 6 positive, and the remaining 93 (23.85%) samples were unclassified due to low/undetected viral load. In this study, we detected the highest percentage (30.89%) of genotype 3 HCV in patients aged 51 to 60 years. The results suggested that genotype 3 HCV is frequently present in Bangladesh and it is usually responses better to interferon therapy. However, genotype 1 and 6 HCV have also been found circulating in this country, which demands longer treatments and effective control measures.

Chromosome 21q deletion syndrome is a rare disorder affecting the long arm of chromosome 21 and manifesting with wide phenotypic features depending on the size and position of the deleted region. In the syndrome, three distinct deleted regions have been distinguished: region 1, from the centromere to approximately 31.2 Mb (21q11.2-q22.11); region 2, from 31.2 to 36 Mb (21q22.11-q22.12); and region 3, from 36 to 37.5 Mb to the telomere (21q22.12-q22.3). The clinical features are highly variable manifesting with mild, poorly recognizable signs or with severe symptoms including craniofacial dysmorphism, growth failure, developmental delay, behavioral/affective abnormalities, and systemic malformations. We report here the case of a young boy with speech delay, mild spastic diplegia, and brain anomalies on magnetic resonance imaging (MRI). The genetic analysis displayed a microdeletion of the long arm of chromosome 21 approximately extending up to 1.08 Mb. Clinical presentation of the patient and cases of 21q21 deletion reported by the literature are discussed.

Hepatitis B virus and hepatitis C virus are the hepatitis subtypes that most commonly induce immune thrombocytopenia (ITP). Although the pathogenesis of viral hepatitis-associated ITP remains unclear, it may involve antibody cross-reactivity due to molecular mimicry, the formation of virus-platelet immune complexes, and T cell-mediated suppression of bone marrow hematopoiesis. Moreover, there is significant correlation between platelet count and the severity of viral hepatitis, the risk of progression to liver cirrhosis, and clinical prognosis. However, treatment of viral hepatitis-associated ITP is hindered by some antiviral drugs. In this review, we summarize research progress to date on the pathogenesis and treatment of viral hepatitis-related ITP, hoping to provide a reference for clinical diagnosis and treatment.

Objective  Our objective was to investigate the concentration of plasma thrombopoietin (TPO) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), as well as its relationship with patients' responses to recombined human TPO (rhTPO) therapy. Methods  We detected the concentration of plasma TPO in 31 patients with AA, 27 patients with MDS, and 11 normal controls using enzyme-linked immunosorbent assay. Results  The median concentration of plasma TPO in patients with AA, MDS, and controls was (841.08 ± 768.64), (212.41 ± 338.93), and (35.09 ± 18.21) pg/mL, respectively. The TPO concentration in patients with AA and MDS was significantly higher than that in controls ( p  < 0.05). The median platelet (PLT) counts were (184 ± 34) ×10 ⁹ /L in the control group and (24 ± 19) ×10 ⁹ /L and (80 ± 71) ×10 ⁹ /L in AA and MDS patients, respectively. Negative correlations were found between plasma TPO concentration and PLT counts as well as megakaryocytes in bone marrow ( p  < 0.05). In AA patients treated with rhTPO, a negative correlation was observed between increased PLT counts and pretreatment TPO levels ( p  < 0.05). Conclusion  Plasma TPO concentration in AA and MDS was significantly higher than that in normal controls. Plasma TPO was negatively correlated with peripheral blood PLT counts and bone marrow megakaryocyte counts. The pretreatment TPO level may serve as a prognostic indicator for the therapeutic effect of rhTPO in AA patients.

Background  Cancer remains a critical global health challenge and a leading cause of mortality. Flavonoids found in fruits and vegetables have gained attention for their potential anti-cancer properties. Fisetin, abundantly present in strawberries, apples, onions, and other plant sources, has emerged as a promising candidate for cancer prevention. Epidemiological studies linking a diet rich in these foods to lower cancer risk have sparked extensive research on fisetin's efficacy. Objective  This review aims to comprehensively explore the molecular mechanisms of fisetin's anticancer properties and investigate its potential synergistic effects with other anticancer drugs. Furthermore, the review examines the therapeutic and preventive effects of fisetin against various cancers. Methods  A systematic analysis of the available scientific literature was conducted, including research articles, clinical trials, and review papers related to fisetin's anticancer properties. Reputable databases were searched, and selected studies were critically evaluated to extract essential information on fisetin's mechanisms of action and its interactions with other anticancer drugs. Results  Preclinical trials have demonstrated that fisetin inhibits cancer cell growth through mechanisms such as cell cycle alteration, induction of apoptosis, and activation of the autophagy signaling pathway. Additionally, fisetin reduces reactive oxygen species levels, contributing to its overall anticancer potential. Investigation of its synergistic effects with other anticancer drugs suggests potential for combination therapies. Conclusion  Fisetin, a bioactive flavonoid abundant in fruits and vegetables, exhibits promising anticancer properties through multiple mechanisms of action. Preclinical trials provide a foundation for further exploration in human clinical trials. Understanding fisetin's molecular mechanisms is vital for developing novel, safe, and effective cancer prevention and treatment strategies. The potential synergy with other anticancer drugs opens new avenues for combination therapies, enhancing cancer management approaches and global health outcomes.

Joubert syndrome (JBTS) is a rare autosomal recessive or X-linked congenital brain malformation with strong genetic heterogeneity. Other neurological features of JBTS include hypotonia, ataxia, developmental delay, and cognitive impairment. Hearing loss with JBTS has been reported in the literature. We present the case of a 3.5-year-old boy born to a healthy consanguineous South Indian couple who was presented with ataxic cerebral palsy (CP) and hearing impairment; medical reports confirmed typical brain malformations of JBTS. Hearing impairment was screened by audiological assessment, which confirmed the presence of severe-profound hearing loss with outer hair cell dysfunction. Whole-exome sequencing (WES) was performed to know the molecular aspects of the condition and to detect any novel mutations. The homozygous mutation AHI1 c.2023G > A associated with JBTS type 3 and GJB2 c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygous AHI1 c.2023G > A and GJB2 c.71G > A in the patient's parents. This study confirms the diagnosis of JBTS by WES helps identify the genetic causes of hereditary disorders that accelerate genetic evaluation and counseling for at-risk families.

Background  Liquid biopsy is mainly used to identify tumor cells in pulmonary neoplasms. It is more often used in research than in clinical practice. The BL-MOL-AR study aims to investigate the efficacy of next-generation sequencing (NGS) and clinical interpretation of the circulating free DNA (cfDNA) levels. This study reports the preliminary results from the first samples analyzed from patients affected by various neoplasms: lung, intestinal, mammary, gastric, biliary, and cutaneous. Methods  The Biopsia Liquida-Molecolare-Arezzo study aims to enroll cancer patients affected by various malignancies, including pulmonary, intestinal, advanced urothelial, biliary, breast, cutaneous, and gastric malignancies. Thirty-nine patients were included in this preliminary report. At time zero, a liquid biopsy is executed, and two types of NGS panels are performed, comprising 17 genes in panel 1, which is already used in the routine tissue setting, and 52 genes in panel 2. From the 7th month after enrollment, 10 sequential liquid biopsies are performed up to the 17th month. The variant allele frequency (%) and cfDNA levels (ng/mL) are measured in every plasmatic sample. Results  The NGS results obtained by different panels are similar even though the number of mutations is more concordant for lung pathologies. There are no significant differences in the actionability levels of the identified variants. Most of the molecular profiles of liquid biopsies reflect tissue data. Conclusions  Preliminary data from this study confirm the need to clarify the limitations and potential of liquid biopsy beyond the lung setting. Overall, parameters related to cfDNA levels and variant allele frequency could provide important indications for prognosis and disease monitoring.

Background  Interleukin-10 (IL-10) is a cytokine with a vast variety of functions, but its role in cancer development and progression is not yet clear. It is involved in two of the hallmarks of cancer: vascularization and immune modulation. IL-10 inhibits angiogenesis and hence is antitumorigenic. But it also can suppress the immune system and be tumorigenic. Objective  Evaluating the role of IL-10 (-1082 A/G) gene promoter single-nucleotide polymorphism (SNP) in breast cancer susceptibility and progression in Georgian women. Methods  A case-control study was performed on a total of 128 women, with 64 of them being histologically confirmed to have breast cancer and 64 healthy controls. SNP genotyping was performed with TaqMan assay with real-time polymerase chain reaction. And pathology report, containing proliferative activity and breast cancer hormonal status, was obtained after surgery of the case individuals. Statistical analysis was done to investigate the significance of data obtained from genotyping and histology reports. Results  Statistical analysis revealed that the difference in frequency of genotypes was not statistically significant between cases and controls (chi-square = 0.5812, p  = 0.7478). The comparison of proliferative activity of cases with AA genotypes and AG/GG genotypes showed no statistical difference ( t  = 0.2575, p  = 0.7980). Although when put into a plot (box and whiskers), patients with AG/GG genotype have outliers with very high proliferative activity. Conclusion  This study shows that -1082 A/G SNP in the promoter region of the IL-10 gene is not associated with breast cancer risk in Georgian women.