A genetic epidemiology study of congenital adrenal hyperplasia in Italy.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD-CAH) is an autosomal recessive disorder affecting steroidogenesis, due to mutations in CYP21A2 (6p21.3). 21OHD-CAH neonatal screening is based on 17-hydroxyprogesterone (17OHP) serum levels, showing high type I error rate and low sensitivity to mild CAH forms.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

What Is Known And Objective: Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia.

Methods: We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses.

Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells.

Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process.

Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease in patients with acute myeloid leukemia.

Invasive fungal diseases (IFD) are still a leading cause of morbidity and mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate dehydrogenase is an enzyme that leads to the production of NADPH, required to destroy microorganisms in the respiratory burst reaction of white blood cells. We evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML patients undergoing intensive chemotherapy.

Charcot-Marie-Tooth disease: genetic subtypes in the Sardinian population.

Charcot-Marie-Tooth disease (CMT) is characterised by great variability of genetic subtypes. This study aimed to assess the genetic subtypes of CMT disease in the Sardinian population. Genetic screening was performed for CMT cases (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]).

Reduced stress granule formation and cell death in fibroblasts with the A382T mutation of TARDBP gene: evidence for loss of TDP-43 nuclear function.

TAR deoxyribonucleic acid-binding protein 43 (TDP-43) is a key protein in the pathogenesis of amyoptrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Recent studies suggest that mutations in the TDP-43 coding gene, TARDBP, as well as variations in TDP-43 protein expression levels may disrupt the dynamics of stress granules (SGs). However, it remains unclear whether the pathogenetic effect of the TDP-43 protein is exerted at the cytoplasmic level, through direct participation to SG composition, or at nuclear level, through control of proteins essential to SG assembly.

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics.

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor.

VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies.

VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model.

Prenatal diagnosis of 1p34.3 interstitial microdeletion by aCGH in a fetus with jaw bone abnormalities.

Background: Interstitial microdeletions in 1p are extremely rare, as very few cases have been reported postnatally and only one prenatally, yet. There is a variability of phenotypic findings such as hypotonia, facial dysmorphisms, mild microcephaly, with being most common developmental delay.

Case Presentation: The present case involved a female fetus with an interstitial deletion on 1p, presenting with micrognathia in the 2nd trimester routine ultrasound examination.

Partial monosomy14q involving FOXG1 and NOVA1 in an infant with microcephaly, seizures and severe developmental delay.

Background: FOXG1 gene mutations have been associated with the congenital variant of Rett syndrome (RTT) since the initial description of two patients in 2008. The on-going accumulation of clinical data suggests that the FOXG1-variant of RTT forms a distinguishable phenotype, consisting mainly of postnatal microcephaly, seizures, hypotonia, developmental delay and corpus callosum agenesis.

Case Presentation: We report a 6-month-old female infant, born at 38 weeks of gestation after in vitro fertilization, who presented with feeding difficulties, irritability and developmental delay from the first months of life.

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients.

We studied telomere length in 32 CML patients who discontinued imatinib after achieving complete molecular remission and 32 age-sex-matched controls. The relative telomere length (RTL) was determined by q-PCR as the telomere to single copy gene (36B4) ratio normalized to a reference sample (K-562 DNA). Age-corrected RTL (acRTL) was also obtained.

An unusual infection in MS patient treated with dimethyl fumarate: A case report of omphalitis.

Background: Notoriously the treatment of multiple sclerosis (MS) is based on the use of several different drugs, characterized by a diverse mechanism of action, efficacy and safety. Recently, progress has been made towards developing new oral immunotherapies, and dimethyl fumarate is the third oral agent approved for the treatment of relapsing-remitting forms.

Case: A 24-year-old patient, affected by relapsing remitting multiple sclerosis, started treatment in December 2014 with dimethyl fumarate.

The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma.

Background: Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs).

Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.

Background: Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses.

Methods And Findings: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls.

Interstitial deletion at 11q14.2-11q22.1 may cause severe learning difficulties, mental retardation and mild heart defects in 13-year old male.

Interstitial deletions of the long arm of chromosome 11 are rare, and they could be assumed as non-recurrent chromosomal rearrangements due to high variability of the size and the breakpoints of the deleted region. The exact region of the deletion was difficult to be determined before the use of molecular cytogenetic techniques such as array comparative genomic hybridization (aCGH). Here, a 13-year old boy with severe learning difficulties, mental retardation and mild heart defects is described.

Killer immunoglobulin-like receptors can predict TKI treatment-free remission in chronic myeloid leukemia patients.

Several factors are predictive of treatment-free remission (TFR) in chronic myeloid leukemia (CML), but few data exist on the role of natural killer (NK) cells and their killer-cell immunoglobulin-like receptors (KIRs). KIR and human leukocyte antigen (HLA) genotypes were investigated in 36 CML patients who discontinued tyrosine kinase inhibitor (TKI) treatment after achieving deep molecular response (MR(4.5)).

Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases.

Objective: This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5-Mb resolution.

Method: A total of 1763 prenatal samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays, BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected by aCGH was assessed, compared with conventional karyotype analysis.

A de novo 2.9 Mb interstitial deletion at 13q12.11 in a child with developmental delay accompanied by mild dysmorphic characteristics.

Background: Proximal deletions in the 13q12.11 region are very rare. Much larger deletions including this region have been described and are associated with complex phenotypes of mental retardation, developmental delay and various others anomalies.

Health-related quality of life in transfusion-dependent patients with myelodysplastic syndromes: a prospective study to assess the impact of iron chelation therapy.

Objective: The primary objective of this study was to evaluate the health-related quality of life (HRQOL) in lower-risk, transfusion-dependent patients with myelodysplastic syndromes (MDS) treated with deferasirox. A secondary objective was to investigate the relationship between HRQOL, serum ferritin levels and transfusion dependency.

Patients And Methods: This was a prospective multicentre study enrolling 159 patients, of whom 152 received at least one dose of deferasirox.

Safe discontinuation of nilotinib in a patient with chronic myeloid leukemia: a case report.

Introduction: Although there is a considerable amount of data in the literature on safe discontinuation of first-generation tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia, little is known about discontinuation of second-generation tyrosine kinase inhibitor therapy. Most previous studies have been focused on dasatinib, and the few cases of nilotinib withdrawal that have been reported had a median follow-up of 12 months. To the best of our knowledge, the present report is the first to describe nilotinib withdrawal with 30 months of follow-up.