Pre genetic diagnosis

AIMS: Alström syndrome (AS) is a rare recessive disorder characterised by diabetes, obesity, insulin resistance (IR), and visual and hearing impairments. Mutations in the ALMS1 gene have been identified as the causative agents of AS. This study aimed to explore the relationship between rare ALMS1 variants and clinical features in Chinese patients with early-onset type 2 diabetes (age at diagnosis ≤40 years; EOD). MATERIALS AND METHODS: ALMS1 gene sequencing was performed in 611 Chinese individuals with EOD, 36 with postprandial hyperinsulinemia, and 47 with pre-diabetes and fasting IR...

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis...

INTRODUCTION: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. AIMS: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC...

Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders. Despite advances in therapies, such as recombinant proteins and products with extended half-lives, the treatment of hemophilia still faces two major limitations: the short duration of therapeutic effect and production of neutralizing antibodies against clotting factors (inhibitor). To overcome these limitations, new hemophilia treatment strategies have been established such as gene therapy, bispecific antibody, and rebalancing therapy...

Traumatic brain injury (TBI) is a frequently encountered form of injury that can have lifelong implications. Despite advances in prevention, diagnosis, monitoring, and treatment, the degree of recovery can vary widely between patients. Much of this is explained by differences in severity of impact and patient-specific comorbidities; however, even among nearly identical patients, stark disparities can arise. Researchers have looked to genetics in recent years as a means of explaining this phenomenon. It has been hypothesized that individual genetic factors can influence initial inflammatory responses, recovery mechanisms, and overall prognoses...

The edgeR (Robust) is a popular approach for identifying differentially expressed genes (DEGs) from RNA-Seq profiles. However, it shows weak performance against gene-specific outliers and is unable to handle missing observations. To address these issues, we proposed a pre-processing approach of RNA-Seq count data by combining the iLOO-based outlier detection and random forest-based missing imputation approach for boosting the performance of edgeR (Robust). Both simulation and real RNA-Seq count data analysis results showed that the proposed edgeR (Robust) outperformed the conventional edgeR (Robust)...

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM...

Growing interest in therapeutic development for rare diseases necessitate a systematic approach to the collection and curation of natural history data that can be applied consistently across this group of heterogenous rare diseases. In this study, we discuss the challenges facing natural history studies for leukodystrophies and detail a novel standardized approach to creating a longitudinal natural history study using existing medical records. Prospective studies are uniquely challenging for rare diseases. Delays in diagnosis and overall rarity limit the timely collection of natural history data...

BACKGROUND: Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) is a rare mitochondrial disease caused by mutations in the GTPBP3 gene. The rare incidence of the disease and the high clinical heterogeneity pose challenges in making a precise diagnosis. Investigations into the rare COXPD23 patients are of pathophysiological and etiological value. In this study, we investigated the genotype-phenotype relationship in a COXPD23 patient from a Manchu family, with GTPBP3 mutations. METHODS: Routine physical examinations, laboratory assays and imaging analyses were performed...

SUMMARY: Thyroid cancer is one of the most common manifestations of Cowden syndrome, yet the syndrome is rare. The incidence of Cowden syndrome is 1 in 200,000. The diagnosis can be made clinically when patients present with a combination of symptoms such as mucocutaneous lesions with a strong personal or family history of thyroid, breast, endometrial, and colorectal cancer. A high index of suspicion is required to provide a clinical diagnosis utilizing major and minor criteria. Once a clinical diagnosis is made, genetic testing for a PTEN mutation, a tumor suppressor gene, is recommended...

BACKGROUND: The length of time from diagnosis of breast cancer to surgery has steadily increased. Consultations and tests, in addition to a lack of available counseling programs, contribute to delays. Evidence suggests that delays between diagnosis and surgery may adversely affect patients. OBJECTIVES: This article examines the effect of time from diagnosis of breast cancer to surgery by requiring nurse navigators to contact the genetic counseling office within 48 hours of the diagnosis to schedule an appointment for the patient as soon as possible...

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality, with metastasis being the primary determinant of poor prognosis in patients. Investigating the molecular mechanisms underlying CRC metastasis is currently a prominent and challenging area of research. Exosomes, as crucial intercellular communication mediators, facilitate the transfer of metabolic and genetic information from cells of origin to recipient cells. Their roles in mediating information exchange between CRC cells and immune cells, fibroblasts, and other cell types are pivotal in reshaping the tumor microenvironment, regulating key biological processes such as invasion, migration, and formation of pre-metastatic niche...

Hepatocellular Carcinoma (HCC) is one of the most common types of primary liver cancer. Current treatment options have limited efficacy against this malignancy, primarily owing to difficulties in early detection and the inherent resistance to existing drugs. Tumor heterogeneity is a pivotal factor contributing significantly to treatment resistance and recurrent manifestations of HCC. Intratumoral heterogeneity is an important aspect of the spectrum of complex tumor heterogeneity and contributes to late diagnosis and treatment failure...

The diversity of genetic and genomic abnormalities observed in acute myeloid leukemia (AML) reflects the complexity of these hematologic neoplasms. The detection of cytogenetic and molecular alterations is fundamental to diagnosis, risk stratification and treatment of AML. Chromosome rearrangements are well established in the diagnostic classification of AML, as are some gene mutations, in several international classification systems. Additionally, the detection of new mutational profiles at relapse and identification of mutations in the pre- and post-transplant settings are illuminating in understanding disease evolution and are relevant to the risk assessment of AML patients...

BACKGROUND: Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. AIMS: We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020...

BACKGROUND AND AIMS: Lynch syndrome (LS) is currently one of the most prevalent hereditary cancer conditions, accounting for 3% of all colorectal cancers and for up to 15% of those with DNA mismatch repair (MMR) deficiency, and it was one of the first historically identified. The understanding of the molecular carcinogenesis of LS tumors has progressed significantly in recent years. We aim to review the most recent advances in LS research and explore genotype-based approaches in surveillance, personalized cancer prevention, and treatment strategies...

BACKGROUND: Prenatal whole exome sequencing (WES) approaches can provide genetic diagnosis with rapid turnaround time and high diagnostic rate when conventional tests are negative. Here we report a family with multiple pregnancy loss and with repeated occurrence of fetal microcephaly. METHODS AND RESULTS: Because of positive family history and recurrent structural abnormality during the pregnancies that may lead postnatal neurodevelopmental consequences, WES analysis was indicated...

BACKGROUND: Identifying individuals with mild cognitive impairment (MCI) at risk of progressing to Alzheimer's disease (AD) provides a unique opportunity for early interventions. Therefore, accurate and long-term prediction of the conversion from MCI to AD is desired but, to date, remains challenging. Here, we developed an interpretable deep learning model featuring a novel design that incorporates interaction effects and multimodality to improve the prediction accuracy and horizon for MCI-to-AD progression...

Lipoblastoma is a very infrequent tumor, characteristic of early childhood. The thoracic location is infrequent, with isolated reports to date. We present the case of a 6-year-old male patient with a right thoracic tumor of months of evolution that was surgically removed by right anterolateral thoracotomy and in which the diagnosis of classic well-differentiated lipoblastoma was histologically confirmed. The patient evolved favorably and was discharged. He is currently under follow-up and without recurrence 1 year after surgery...

KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S2MMAM). S2MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2MF-CN)...