MicroRNA dysregulation in ataxia telangiectasia.

Introduction: Ataxia telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, a predisposition to malignancies, and high clinical variability. Profiling of microRNAs (miRNAs) may offer insights into the underlying mechanisms of complex rare human diseases, as miRNAs play a role in various biological functions including proliferation, differentiation, and DNA repair. In this study, we investigate the differential expression of miRNAs in samples from AT patients to identify miRNA patterns and analyze how these patterns are related to the disease.

Efficient wastewater sample filtration improves the detection of SARS-CoV-2 variants: An extensive analysis based on sequencing parameters.

During the SARS-CoV-2 pandemic, many countries established wastewater (WW) surveillance to objectively monitor the level of infection within the population. As new variants continue to emerge, it has become clear that WW surveillance is an essential tool for the early detection of variants. The EU Commission published a recommendation suggesting an approach to establish surveillance of SARS-CoV-2 and its variants in WW, besides specifying the methodology for WW concentration and RNA extraction.

Analysis of the DNA methylation pattern of the promoter region of calcitonin gene-related peptide 1 gene in patients with episodic migraine: An exploratory case-control study.

Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of gene in patients with episodic migraine.

Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia.

Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels.

Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders.

Objective: To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders.

Study Design: A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations.

Parental counseling in trisomy 18: Novel insights in prenatal features and postnatal survival.

Data on the outcome of trisomy T18 (T18) when diagnosed during pregnancy are lacking. We performed a retrospective study of pregnancies complicated by T18 diagnosed at our center and a literature search for publications on the topic, with pooled estimates of survival rates at different gestational and post-natal ages. In our series, all the 60 patients included in the analysis had prenatally detected ultrasound anomalies, which were evidenced in the first trimester or at the second trimester scan in 73% of cases.

An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2.

Background: Hereditary ataxias are a heterogeneous group of neurodegenerative disorders, where exome sequencing may become an important diagnostic tool to solve clinically or genetically complex cases.

Methods: We describe an Italian family in which three sisters were affected by ataxia with postural/intentional myoclonus and involuntary movements at onset, which persisted during the disease. Oculomotor apraxia was absent.

Blood metal levels and related antioxidant enzyme activities in patients with ataxia telangiectasia.

Transition metals are cofactors for a wide range of vital enzymes and are directly or indirectly involved in the response against reactive oxygen species (ROS), which can damage cellular components. Their altered homeostasis has been studied in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), but no data are available on rarer conditions. We aimed at studying the role of essential trace elements in ataxia telangiectasia (A-T), a rare form of pediatric autosomal recessive cerebellar ataxia with altered antioxidant response.

Deep-intronic ATM mutation detected by genomic resequencing and corrected in vitro by antisense morpholino oligonucleotide (AMO).

Recent development of next-generation DNA sequencing (NGS) techniques is changing the approach to search for mutations in human genetic diseases. We applied NGS to study an A-T patient in which one of the two expected mutations was not found after DHPLC, cDNA sequencing and MLPA screening. The 160-kb ATM genomic region was divided into 31 partially overlapping fragments of 4-6 kb and amplified by long-range PCR in the patient and mother, who carried the same mutation by segregation.

Maternal polymorphisms for methyltetrahydrofolate reductase and methionine synthetase reductase and risk of children with Down syndrome.

Objective: The purpose of this research was to study factors that are involved in centromeric hypomethylation in the pathogenesis of Down syndrome (DS).

Study Design: This was a case-control study to evaluate the association between methyltetrahydrofolate reductase (MTHFR) C677T and methionine synthetase-reductase (MTRR) A66G polymorphisms and the risk of DS; we compared mothers in Italy who had children with DS and matched control subjects.

Results: Seventy-four cases of DS caused by an error in maternal meiosis were compared with 184 matched control subjects.

Risk assessment for Down syndrome with genetic sonogram in women at risk.

Objective: To evaluate the algorithms of risk assessment for Down syndrome (DS).

Methods: Cohort study conducted in women at risk undergoing midtrimester genetic sonogram. Univariate and logistic regression analysis were used to relate findings to the occurrence of DS.

Identifying the causes of stillbirth: a comparison of four classification systems.

Objective: To identify the classification protocol for stillbirth that minimizes the rate of unexplained causes.

Study Design: All stillbirths at > 22 weeks from 1995-2007 underwent a workup inclusive of fetal ultrasonography, amniocentesis for karyotype and cultures, placental histology, fetal autopsy, skin biopsy, total body X-ray, maternal testing for thrombophilias, TORCH, Parvovirus spp, thyroid function, indirect Coombs, Kleiheuer-Betke test, and genital cultures. To such a cohort, we applied the 4 most commonly used classification protocols.

Preterm twins: what threshold of birth weight discordance heralds major adverse neonatal outcome?

Objective: This study was undertaken to establish the optimal threshold of birth weight discordance for prediction of adverse outcome in liveborn, non-malformed preterm twins.

Study Design: We accessed a cohort of twin gestations for the period 1990 through 2000 delivered at less than 37.0 weeks' gestation.

Doppler predictors of adverse neonatal outcome in the growth restricted fetus at 34 weeks' gestation or beyond.

Objective: The study was undertaken to assess whether prenatal Doppler variables can identify cases of fetal growth restriction (FGR) approaching term who are at risk for adverse neonatal outcome.

Study Design: From a cohort of FGR cases delivered at >or=34 weeks, fetal biometry and pulsatility indices (PI) of fetal arteries obtained less than 2 weeks before delivery were related to adverse neonatal outcome, defined as admission to the neonatal intensive care unit (NICU) for indications other than low birth weight alone.

Results: Stepwise regression analysis showed that after controlling for gestational age at delivery and fetal biometry, only the last umbilical artery (UA) PI percentile was significantly predictive of adverse neonatal outcome (odds ratio=1.