Novel and recurrent genetic variants associated with male and female infertility.

Recently, the knowledge of the genetic basis of fertility disorders has expanded enormously, mainly thanks to the use of next-generation sequencing (NGS). However, the genetic cause of infertility, in the majority of patients, is still undefined. The aim was to identify novel and recurrent pathogenic/likely pathogenic variants in patients with isolated infertility or puberty delay using a targeted NGS technique.

Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

Molecular analysis of inherited disorders of cornification in polish patients show novel variants and functional data and provokes questions on the significance of secondary findings.

Background: The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases.

Hypogonadism - when does genetic diagnosis help in therapy?

Objectives: The objective of the study was to describe phenotype-genotype correlation in selected cases with infertility and emphasise the importance of genetic testing as useful tool for proper treatment decision making MATERIAL AND METHODS: Genetic tests were performed in four patients as a part of diagnostic procedure by Sanger sequencing or targeted next generation sequencing (NGS gene panel).

Results: We found the genetic causes of hypogonadotropic hypogonadism in 3 males and female with infertility.

Conclusions: Genetic testing is carried out when searching for the genetic causes of clinically identified disorders.

Congenital coenzyme Q5-linked pathology: causal genetic association, core phenotype, and molecular mechanism.

Coenzyme Q5 (COQ5), a C-methyltransferase, modifies coenzyme Q10 (COQ10) during biosynthesis and interacts with polyA-tail regulating zinc-finger protein ZC3H14 in neural development. Here, we present a fifth patient (a third family) worldwide with neurodevelopmental and physiological symptoms including COQ10 deficiency. Our patient harbors one novel c.

Addressing HIV and Homelessness During COVID-19: A Community-Based Demonstration Project.

People experiencing homelessness are at increased risk for HIV, and people with HIV (PWH) experiencing homelessness are more likely to experience suboptimal HIV health outcomes than PWH with stable housing. Within Alabama, a state prioritized in the Ending the HIV Epidemic initiative, Jefferson County consistently has the highest number of new HIV diagnoses as well as a high percentage of the state's homeless population. To address the twin epidemics of both HIV and homelessness within the high-priority setting of Jefferson County, Alabama, this 1-year community-based project, Ending the HIV Epidemic: Addressing HIV Health and Homelessness (AH3), sought to increase HIV testing and linkage to care among this population by placing a full-time case manager trained in HIV testing and case management at a homeless shelter.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

Background: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally.

The retrospective molecular analysis of large or giant congenital melanocytic nevi in a group of Polish children.

Background: Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of and genes in resection specimens from large or giant CMN in a group of Polish patients.

Genetic Risk Factors in Early-Onset Nonalcoholic Chronic Pancreatitis: An Update.

Chronic pancreatitis (CP) is a progressive, irreversible inflammatory disorder of the pancreas, which results from interrelations between different genetic and environmental factors. Genetic variants are the primary cause of the disease in early-onset nonalcoholic CP patients. Novel CP-associated genes are continuously emerging from genetic studies on CP cohorts, providing important clues for distinct mechanisms involved in CP development.

The genetic basis of classical galactosaemia in Polish patients.

Classic galactosemia (OMIM #230400) is an autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the galactose-1-phosphate uridylyltransferase gene (GALT; 606999) on chromosome 9p13. Its diagnosis is established by detecting elevated erythrocyte galactose-1-phosphate concentration, reduced erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity. Biallelic pathogenic variants in the GALT gene is confirmed by DNA analysis.

Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Purpose: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported.

Methods: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks.

Cetuximab in Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Ovarian Cancer Without KRAS, NRAS, or BRAF Mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Background: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets.

Objective: With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations.

Patients And Methods: Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m over 60 min).

Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) with FLT-3 Amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Background: TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor of FMS-like tyrosine kinase-3 (FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT-3 amplification treated with sunitinib are reported.

Chronic pancreatitis caused by a Homozygous c.194 + 2T > C variant and Pancreas Divisum in a 3-year-old child-case report.

Chronic pancreatitis (CP) is a rare disease in children. We describe the first case of a 3-year-old Caucasian patient with CP with the presence of a homozygous pathogenic variant c.194 + 2T > C in ( ) and pancreas divisum.

The Y-chromosome F haplogroup contributes to the development of Barrett's esophagus-associated esophageal adenocarcinoma in a white male population.

Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males.

Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease.

Hailey-Hailey disease (HHD) is a rare, late-onset autosomal dominant genodermatosis characterized by blisters, vesicular lesions, crusted erosions, and erythematous scaly plaques predominantly in intertriginous regions. HHD is caused by ATP2C1 mutations. About 180 distinct mutations have been identified so far; however, data of only few cases from Central Europe are available.

Palbociclib in Patients With Pancreatic and Biliary Cancer With Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Purpose: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study identifies signals of antitumor activity of commercially available targeted agents in patients with advanced cancers that harbor genomic alterations known as drug targets. In this article, data from two cohorts of patients with pancreatic and biliary cancers with loss or mutation treated with palbociclib are reported.

Methods: Eligible patients age 12 years and older with advanced measurable or evaluable solid tumors are provided treatment according to protocol-specified genomic matching rules.