On the Permissibility of Homicidal Violence: Perspectives from Former U.S. White Supremacists.

Drawing upon in-depth life-history interviews with 91 North American-based former white supremacists, we examine how participants perceive homicidal violence as either an appropriate or inappropriate political strategy. Based on the current findings, participants considered homicidal violence as largely inappropriate due to moral concerns and its politically ineffective nature but also discussed how homicidal violence could be an appropriate defensive measure in RAHOWA (Racial Holy War) or through divine mandate. Capturing how white supremacists frame the permissibility of homicidal violence is a step toward better understanding the "upper limit" or thresholds for violence among members who are trying to construct and negotiate a collective identity that involves violent and aggressive worldviews.

DPYD*6 plays an important role in fluoropyrimidine toxicity in addition to DPYD*2A and c.2846A>T: a comprehensive analysis in 1254 patients.

Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.

Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia.

Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive genetic disorder characterised by dysfunction of motile cilia. Ciliary dysmotility causes poor mucociliary clearance and leads to impairment of pulmonary function and severe respiratory infections. PCD has no specific therapy.

Uncommon dihydropyrimidine dehydrogenase mutations and toxicity by fluoropyrimidines: a lethal case with a new variant.

DPD is the rate-limiting enzyme involved in the metabolism of 5-fluorouracil and its prodrugs, capecitabine and tegafur. Many cases of severe toxicities by fluoropyrimidines are reported in the literature, sometimes with lethal outcome, due to a poor or null metabolizer phenotype. The exon 14-skipping mutation IVS14+1G>A and the c.

625 kb microduplication at Xp22.12 including RPS6KA3 in a child with mild intellectual disability.

Here, we report on a patient with a 625 kb duplication in Xp22.12, detected by array comparative genomic hybridization (CGH). The duplicated region contains only one gene, RPS6KA3, that results in partial duplication.

Discovery of novel mutations in the dihydropyrimidine dehydrogenase gene associated with toxicity of fluoropyrimidines and viewpoint on preemptive pharmacogenetic screening in patients.

Background: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of the metabolic pathway of 5-fluorouracil (5-FU) and other fluoropyrimidines to inactive compounds. For this reason, severe, life-threatening toxicities may occur in patients with deficient DPD activity when administered standard doses of 5-FU and its prodrugs.

Materials And Methods: We selected three patients with colorectal adenocarcinoma who displayed unexpected severe adverse reactions after treatment with 5-FU and capecitabine.

17q12 microduplications: a challenge for clinicians.

In the recent years, some cases of 17q12 deletions and duplications have been reported, but the clinical impact of these imbalances is still to be fully elucidated. In particular, 17q12 duplications elude syndrome classification, since they are associated with a wide phenotypic spectrum, ranging from very mild to quite severe phenotypes. Here, two unrelated patients with the same 1.

Valproate Treatment in an ALS Patient Carrying a c.194G>A Spastin Mutation and SMN2 Homozygous Deletion.

Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600 mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism.

Mannose-binding lectin 2 gene polymorphism and lung damage in primary ciliary dyskinesia.

Background: Mannose-binding lectin (MBL) plays an important role in innate immunity and has been reported to be associated with the age-related decline in lung function in cystic fibrosis.

Hypothesis: MBL polymorphisms are associated with lung function decline in Primary Ciliary Dyskinesia (PCD).

Methods: We performed sputum microbiology, spirometry pre- and post-administration of salbutamol, ciliary motion analysis, ultrastructural assessment of cilia, ciliogenesis in culture, and chest high resolution computed tomography in children with a clinical history of respiratory tract infections and/or presence of bronchiectasis suggestive of PCD or secondary ciliary dyskinesia (SCD).

Hereditary spastic paraparesis in adults. A clinical and genetic perspective from Tuscany.

Objective: Hereditary spastic paraparesis or paraplegias (HSPs) are a group of neurogenetic conditions with prominent involvement of the pyramidal tracts. Aim of this study is the clinical and molecular characterization of a cohort of patients with HSP. Moreover, we aim to study the minimum prevalence of HSP in our area and to propose a schematic diagnostic approach to HSP patients based on the available data from the literature.

NR5A1 gene mutations: clinical, endocrine and genetic features in two girls with 46,XY disorder of sex development.

Background: Steroidogenic factor 1, encoded by the NR5A1 gene, is a key regulator of endocrine function within the hypothalamic-pituitary-steroidogenic axis. Both homozygous, compound heterozygous and heterozygous mutations in the NR5A1 gene may determine 46,XY disorders of sex development (DSD).

Patients And Methods: NR5A1 gene sequencing was performed in a cohort of 6 patients with 46,XY DSD without specific diagnosis.

Benign cephalic histiocytosis.

A one and a half year old girl born of a non-consanguineous marriage presented with multiple asymptomatic erythematous to hyperpigmented and skin colored papules on both cheeks slowly increasing in number of 1 year duration. On the basis of clinical, histopathological, and immunohistochemistry findings, a diagnosis of benign cephalic histiocytosis was made.

Penile pyoderma gangrenosum.

A 70-year-old man presented with indurated penile ulcers of 1-month duration. Initial biopsy was reported as chronic ulcer. A repeat biopsy done due to inadequate response to doxycycline showed features of pyoderma gangrenosum.

Role of 18F-DOPA PET/CT in diagnosis and follow-up of adrenal and extra-adrenal paragangliomas.

Purpose: The objective of this study was to establish the clinical value of F-DOPA PET/CT in patients with adrenal and extra-adrenal paragangliomas (PGLs).

Methods: Twenty-six consecutive patients with suspected or recurrent PGL underwent MR (and/or CT) and F-DOPA PET/CT. Histopathology confirmation was obtained in 20 cases.

FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer.

Background: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 4-6months with first-line conventional treatments. Our group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognosis subgroup. The aim of this work was to prospectively validate our retrospective finding.

Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation.

We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers.

Clofazimine-induced Hair Pigmentation.

A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy.

Clinical characteristics and genetic analysis in women with premature ovarian insufficiency.

Objective: Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism.

Methods: We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29 years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography.

Acro-cardio-facial syndrome: a microdeletion syndrome?

Acro-cardio-facial syndrome (ACFS) is an infrequently reported, variable condition characterized by split-hand and split-foot malformation and congenital heart defect (CHD), along with cleft lip and palate, genital anomalies, unusual face and intellectual disability. An autosomal recessive pattern of inheritance has been suggested because of affected sibs born to unaffected parents and parental consanguinity; the cause is unknown. We describe a newborn with the clinical manifestations of ACFS in whom a deletion of the region 6q21-q22.

An idic(15) associated with POF (premature ovarian failure): molecular cytogenetic definition of a case and review of the literature.

We report on a 36-year-old infertile woman, presenting a premature ovarian failure with an otherwise normal female phenotype. Cytogenetic analyses showed the presence of a supernumerary marker chromosome, that was characterized by FISH (fluorescent in situ hybridization) and array CGH (comparative genomic hybridization). This marker chromosome was derived from chromosome 15, and contained only heterochromatic material.

Molecular cytogenetic characterization of an interstitial deletion of chromosome 21 (21q22.13q22.3) in a patient with dysmorphic features, intellectual disability and severe generalized epilepsy.

We report on a de novo interstitial deletion of chromosome 21q in a patient presenting with characteristic facial features, intellectual disability, and epilepsy. The deletion extent was about 4.9 Mb from position 37713441 bp (21q22.

Sporadic or familial head neck paragangliomas enrolled in a single center: clinical presentation and genotype/phenotype correlations.

Background: The purpose of this study was to investigate clinical features and prevalence of germline mutations of patients with head/neck paragangliomas.

Methods: Genetic analysis on known susceptibility genes for paragangliomas (VHL, RET, SDHB, SDHC, SDHD, and SDHAF2) was performed in 17 consecutive patients with head/neck paraganglioma (age range, 14-82 years) and 17 relatives.

Results: Head/neck paragangliomas were usually symptomatic with "mass effect" (88.

IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene.

Background: Short stature represents one of the main features of children with Noonan syndrome. The reason for impaired growth remains largely unknown.

Objective: To assess GH and IGF1 secretion in children with Noonan syndrome.