Spherocytosis in Newborn Secondary to Novel Heterozygous Mutation in Gene: Case Report.

This case report describes a novel mutation of the gene as a potential pathogenic cause of spherocytosis. A 3-week-old male presented with clinical and laboratory signs consistent with hemolytic spherocytosis, including jaundice, hyperbilirubinemia, anemia, reticulocytosis, negative Coombs test, no ABO or Rh incompatibility, and a peripheral blood smear notable for numerous spherocytes. His laboratory work demonstrated persistent anemia despite daily folate prompting next-generation sequencing which revealed a novel mutation in the gene resulting in a nonfunctioning protein product.

Quantitative dopamine transporter imaging assessment in Parkinson's disease patients carrying GBA gene mutations compared with idiopathic PD patients: A case-control study.

Background: Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative-based data, various studies have been published on GBA-PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei.

Methods: This retrospective study included two consecutive homogenous cohorts of GBA-PD and idiopathic (I-PD) patients.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging.

Six new cases of CRB2-related syndrome and a review of clinical findings in 28 reported patients.

The Crumbs homolog-2 (CRB2)-related syndrome (CRBS-RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha-fetoprotein levels in maternal serum and amniotic fluid. CRB2-related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-RS have highlighted renal disease with persistent proteinuria and steroid-resistant nephrotic syndrome (SRNS).

UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.

Purpose: The human chromosome 19q13.11 deletion syndrome is associated with a variable phenotype that includes aplasia cutis congenita (ACC) and ectrodactyly as specific features. UBA2 (ubiquitin-like modifier-activating enzyme 2) lies adjacent to the minimal deletion overlap region.

Biallelic disruption of is associated with a skeletal disorder characterised by rhizomelic shortening of extremities and dysmorphic features.

Background: During mouse embryonic development the protein kinase domain containing, cytoplasmic () gene, also known as is expressed in several tissues including the ventral midbrain, with particularly strong expression in branchial arches and limb buds. Homozygous knockout mice have dysmorphic features and shortened long bones as the most obvious morphological abnormalities. The human gene has currently not been associated with any disorders.

Utility and limitations of exome sequencing as a genetic diagnostic tool for children with hearing loss.

Purpose: Hearing loss (HL) is the most common sensory disorder in children. Prompt molecular diagnosis may guide screening and management, especially in syndromic cases when HL is the single presenting feature. Exome sequencing (ES) is an appealing diagnostic tool for HL as the genetic causes are highly heterogeneous.

Utility and limitations of exome sequencing as a genetic diagnostic tool for conditions associated with pediatric sudden cardiac arrest/sudden cardiac death.

Background: Conditions associated with sudden cardiac arrest/death (SCA/D) in youth often have a genetic etiology. While SCA/D is uncommon, a pro-active family screening approach may identify these inherited structural and electrical abnormalities prior to symptomatic events and allow appropriate surveillance and treatment. This study investigated the diagnostic utility of exome sequencing (ES) by evaluating the capture and coverage of genes related to SCA/D.

Epigenome-derived drugs: recent advances and future perspectives.

This review highlights the current knowledge of epigenetic targets of anticancer therapy and outlines the current limitations of epigenetic approaches and the difficulties in defining preventive tools and strategies. Promising strategies towards achieving the goal of developing effective epigenetic treatments are discussed, including restoration or enhancement of sensitivity to other treatment modalities, and combinations with other agents and new therapeutic areas.

Characterization of a novel satellite DNA sequence from Flying Dragon (Poncirus trifoliata).

Repetitive sequences constitute a significant component of most eukaryotic genomes, and the isolation and characterization of repetitive DNA sequences provide an insight into the organization of the genome of interest. Here, we report the isolation and the molecular analysis and methylation status of a novel tandemly organized repetitive DNA sequence from the genome of Poncirus trifoliata. Digestion of P.

Different patterns of extracellular matrix protein expression in the convexity and the concavity of the dilated aorta with bicuspid aortic valve: preliminary results.

Objective: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease.

Methods: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling.

DNA methylation 40 years later: Its role in human health and disease.

A long path, initiated more than 40 years ago, has led to a deeper understanding of the complexity of gene regulation in eukaryotic genomes. In addition to genetic mechanisms, the imbalance in the epigenetic control of gene expression may profoundly alter the finely tuned machinery leading to gene regulation. Here, we review the impact of the studies on DNA methylation, the "primadonna" in the epigenetic scenario, on the understanding of basic phenomena, such as X inactivation and genomic imprinting.

The mutation spectrum of the APC gene in FAP patients from southern Italy: detection of known and four novel mutations.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition accounting for about 1% of all colorectal cancers, results from mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and severity of FAP varies greatly with the mutation site, and both between and within families. Using the protein truncation test, single strand conformation polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles in 40 unrelated FAP families, for a total of 22 different APC mutations.