Case report: A single novel calpain 3 gene variant associated with mild myopathy.

Recessively inherited limb-girdle muscular dystrophy type 1, caused by mutations in the calpain 3 gene, is the most common limb-girdle muscular dystrophy worldwide. Recently, cases of autosomal dominant calpainopathy have been described. A man was referred to our neurological outpatient clinic at the age of 54 for persistent hyperCKemia (>1000 U/l) associated with muscle fatigue and myalgia.

Genetics architecture of spontaneous coronary artery dissection in an Italian cohort.

Spontaneous coronary artery dissection (SCAD) is a relevant non-atherosclerotic cause of acute coronary syndrome with a complex genetic architecture. Recent discoveries have highlighted the potential role of miRNAs and protein-coding genes involved in the processing of small RNAs in the pathogenesis of SCAD. Furthermore, there may be a connection between SCAD and the increased cardiovascular risk observed in fragile X premutation carriers as well as a correlation with pathogenetic variants in genes encoding for collagen and extracellular matrix, which are related to connective tissue disorders (CTDs).

The neurological core features of the infantile-onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family.

Aim: Biallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features.

Next-generation sequencing in Charcot-Marie-Tooth: a proposal for improvement of ACMG guidelines for variant evaluation.

Background: The application of massive parallel sequencing technologies in the molecular analysis of Charcot-Marie-Tooth (CMT) has enabled the rapid and cost-effective identification of numerous potentially significant variants for diagnostic purposes. The objective is to reduce the number of variants, focusing only on those with pathogenic significance. The 2015 American College of Medical Genetics and Genomics (ACMG) guidelines aid in achieving this goal, but it is now evident that a pathology or gene-specific review of these rules is essential to avoid misinterpretations that may result from blindly applying the criteria.

Early Onset Inherited Peripheral Neuropathies: The Experience of a Specialized Referral Center for Genetic Diagnosis Achievement.

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies. Although the typical disease onset is reported in the second decade, earlier onsets are not uncommon. To date, few studies on pediatric populations have been conducted and the achievement of molecular diagnosis remains challenging.

Skeletal muscle involvement in biallelic mutations: case report and review of the literature.

Biallelic mutations in the sorbitol dehydrogenase () gene have been identified as a genetic cause of autosomal recessive axonal Charcot-Marie-Tooth disease 2 (CMT2) and distal hereditary motor neuropathy (dHMN). We herein review the main phenotypes associated with mutations and report the case of a 16-year-old man who was referred to our outpatient clinic for a slowly worsening gait disorder with wasting and weakness of distal lower limbs musculature. Since creatine phosphokinase (CPK) values were persistently raised (1.

Case report: Episodic ataxia without ataxia?

Hereditary myopathies represent a clinically and genetically heterogeneous group of neuromuscular disorders, characterized by highly variable clinical presentations and frequently overlapping phenotypes with other neuromuscular disorders, likely influenced by genetic and environmental modifiers. Genetic testing is often challenging due to ambiguous clinical diagnosis. Here, we present the case of a family with clinical and Electromyography (EMG) features resembling a myotonia-like disorder in which Whole Exome Sequencing (WES) analysis revealed the co-segregation of two rare missense variants in and , genes previously associated with episodic ataxia 8 (EA8).

A novel de novo variant in POLR3B gene associated with a primary axonal involvement of the largest nerve fibers.

Background And Aims: POLR3B gene encodes a subunit of RNA polymerase III (Pol III). Biallelic mutations in POLR3B are associated with leukodystrophies, but recently de novo heterozygous mutations have been described in early onset peripheral demyelinating neuropathies with or without central involvement. Here, we report the first Italian case carrying a de novo variant in POLR3B with a pure neuropathy phenotype and primary axonal involvement of the largest nerve fibers.

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia.

Introduction/aims: Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition.

Methods: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study.

Secondary Somatic Mutations in G-Protein-Related Pathways and Mutation Signatures in Uveal Melanoma.

Background: Uveal melanoma (UM), a rare cancer of the eye, is characterized by initiating mutations in the genes G-protein subunit alpha Q (), G-protein subunit alpha 11 (), cysteinyl leukotriene receptor 2 (), and phospholipase C beta 4 () and by metastasis-promoting mutations in the genes splicing factor 3B1 (), serine and arginine rich splicing factor 2 (SRSF2), and BRCA1-associated protein 1 (). Here, we tested the hypothesis that additional mutations, though occurring in only a few cases ("secondary drivers"), might influence tumor development.

Methods: We analyzed all the 4125 mutations detected in exome sequencing datasets, comprising a total of 139 Ums, and tested the enrichment of secondary drivers in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that also contained the initiating mutations.

Prognostic value of chromosomal imbalances, gene mutations, and BAP1 expression in uveal melanoma.

Uveal melanoma (UM) exhibits recurring chromosomal abnormalities and gene driver mutations, which are related to tumor evolution/progression. Almost half of the patients with UM develop distant metastases, predominantly to the liver, and so far there are no effective adjuvant therapies. An accurate UM genetic profile could assess the individual patient's metastatic risk, and provide the basis to determine an individualized targeted therapeutic strategy for each UM patient.

Utility of low mA 1.5 pitch helical versus conventional high mA abdominal CT.

The objective of this study was to evaluate the utility of a low mA 1.5 pitch helical versus conventional high mA conventional technique in abdominal computed tomography (CT). Twenty-five patients who had both a conventional high mA (> 300) and a 1.

Extended pitch thoracic helical CT 47.

The objective of this study was to test whether extended 1.5 pitch helical computed tomography (CT) can be used for routine thoracic CT without a significant loss of clinical scan quality. Thirty consecutive patients presenting for contrast thoracic CT were computer randomized into one of three groups: conventional, 1.

Comparison of 1.0-, 1.5-, and 2.0-pitch abdominal helical computed tomography in evaluation of normal structures and pathologic lesions.

Rationale And Objectives: The authors performed a comprehensive prospective clinical trial comparing 1.0-, 1.5-, and 2.

Multiplanar image reconstruction and 3D imaging using a musculoskeletal phantom: conventional versus helical CT.

Purpose: Our goal was to perform a detailed comparison of the relative performances of helical CT (pitches 1.0, 1.5, and 2.

Routine use of a higher order interpolator and bone algorithm in thoracic CT.

Objective: This study was designed to evaluate the utility of the routine use of high spatial frequency algorithms and higher order helical interpolators for imaging lung parenchyma during routine thoracic CT.

Subjects And Methods: We evaluated 50 consecutive patients undergoing clinically indicated thoracic CT using the same imaging parameters and scanner. The helical volume was reconstructed three separate times using standard and higher order (180 degrees linear with double-sided lobes) interpolators and standard and high spatial frequency (bone) algorithms.

[Role of echography in the diagnosis of visceral ischemic syndrome].

Personal experience of the current possibilities of ultrasonography in the diagnosis of visceral ischaemic syndrome is reported.

[Intramural diverticulosis of the gallbladder].

The authors report on 9 cases of acalculous adenomyomatosis of the gallbladder, selected to Arianoff's classification. The clinical, anatomopathological and radiological data are considered: there isn't difference concerning the clinical symptoms between adenomyomatosis and cholelithiasis; only radiological study may clarify the nature and character of these lesions. The authors conclude stressing the importance of surgical therapy because the medical therapy is only symptomatic and does not modify the natural evolution of the disease and its complications.