Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors.

Survival rates of childhood cancer patients have improved over the past four decades, although cancer treatments increase the risk of developing chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in childhood cancer survivors (CCS). Biochemical, proteomic, and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, the results being compared with those obtained on MNCs of 154 healthy subjects.

Discrete Changes in Glucose Metabolism Define Aging.

Aging is a physiological process in which multifactorial processes determine a progressive decline. Several alterations contribute to the aging process, including telomere shortening, oxidative stress, deregulated autophagy and epigenetic modifications. In some cases, these alterations are so linked with the aging process that it is possible predict the age of a person on the basis of the modification of one specific pathway, as proposed by Horwath and his aging clock based on DNA methylation.

Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic Progenitors Compared to Term Samples.

Background: Cord blood contains high number of hematopoietic cells that after birth disappear. In this paper we have studied the functional properties of the umbilical cord blood progenitor cells collected from term and preterm neonates to establish whether quantitative and/or qualitative differences exist between the two groups.

Methods And Results: Our results indicate that the percentage of total CD34+ cells was significantly higher in preterm infants compared to full term: 0.

Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.

Background: Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet.

Methods: We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new.

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene.

Introduction: Congenital analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. It is an allelic heterogeneous defect, caused by variety of mutations within the albumin gene in homozygous or compound heterozygous state. Herein we report the clinical and molecular characterization of a new case of congenital analbuminemia diagnosed in a female newborn of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (< 8 g/L) and severe clinical symptoms.

Mutations in DSTYK and dominant urinary tract malformations.

Background: Congenital abnormalities of the kidney and the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and the etiologic factors are poorly understood.

Methods: We performed genomewide linkage analysis and whole-exome sequencing in a family with an autosomal dominant form of congenital abnormalities of the kidney or urinary tract (seven affected family members).

A novel mutation in the albumin gene (c.1A>C) resulting in analbuminemia.

Background: Analbuminemia (OMIM # 103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene.

Design: We report here the clinical and molecular characterisation of two new cases of congenital analbuminemia diagnosed in two members of the Druze population living in a Galilean village (Northern Israel) on the basis of their low level of circulating albumin.

A novel splicing mutation causes analbuminemia in a Portuguese boy.

Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was suspected in a Portuguese boy who presented with low albumin level (about 3.

Molecular diagnosis of analbuminemia: a new case caused by a nonsense mutation in the albumin gene.

Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction.

Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome.

To identify gene loci associated with steroid-resistant nephrotic syndrome (SRNS), we utilized homozygosity mapping and exome sequencing in a consanguineous pedigree with three affected siblings. High-density genotyping identified three segments of homozygosity spanning 33.6 Mb on chromosomes 5, 10, and 15 containing 296 candidate genes.

Mutations in SOX17 are associated with congenital anomalies of the kidney and the urinary tract.

Congenital anomalies of the kidney and the urinary tract (CAKUT) represent a major source of morbidity and mortality in children. Several factors (PAX, SOX,WNT, RET, GDFN, and others) play critical roles during the differentiation process that leads to the formation of nephron epithelia. We have identified mutations in SOX17, an HMG-box transcription factor and Wnt signaling antagonist, in eight patients with CAKUT (seven vesico-ureteric reflux, one pelvic obstruction).

A novel frameshift deletion in the albumin gene causes analbuminemia in a young Turkish woman.

Background: Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. The analbuminemic trait was diagnosed in a young Turkish woman on the basis of her clinical symptoms (bilateral lower limb edema) and biochemical findings (minimal albumin amount and variable increases in other protein fractions).

Methods: Total DNA from the analbuminemic proband and her parents was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the albumin gene (ALB) and the flanking intron regions.

A novel frame-shift deletion causing analbuminaemia in an Italian paediatric patient.

Background: Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene.

Design: We report here the clinical and molecular characterization of a new case of congenital analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10.

A novel WT1 gene mutation in a three-generation family with progressive isolated focal segmental glomerulosclerosis.

Background And Objectives: Wilms tumor-suppressor gene-1 (WT1) plays a key role in kidney development and function. WT1 mutations usually occur in exons 8 and 9 and are associated with Denys-Drash, or in intron 9 and are associated with Frasier syndrome. However, overlapping clinical and molecular features have been reported.

Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.

Background And Objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS.

Design, Setting, Participants, & Measurements: We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33).

Analbuminemia in a Swedish male is caused by the Kayseri mutation (c228_229delAT).

Background: Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. Here we report the first case of hereditary analbuminemia in the ethnic Swedish population, and we define the molecular defect that causes the analbuminemic trait.

Methods: Total DNA, extracted from peripheral blood samples from the analbuminemic proband and his parents, was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons, the exon-intron splice junctions, and the 5' and 3' untranslated regions of the albumin gene.

Analbuminemia Zonguldak: case report and mutational analysis.

Objectives: To document a new case of the rare disease analbuminemia and to study the molecular defect responsible for the trait.

Design And Methods: Single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing of the 14 exons and their flanking intron regions, as well as of the 5' and 3' UTR, of the albumin gene were conducted on DNA extracted from peripheral blood samples.

Results: DNA sequence analysis showed that the proband was homozygous, and his parents were both heterozygous, for a previously unreported 5180 T-->A transversion.

Analbuminemia produced by a novel splicing mutation.

Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating human serum albumin in homozygous or compound heterozygous individuals. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was diagnosed in a Turkish female infant on the basis of low albumin concentration ( approximately 9.

HIV risk, systemic inequities, and Aboriginal youth: widening the circle for HIV prevention programming.

Background: In Canada, Aboriginal people are overrepresented in the HIV epidemic and infected at a younger age than non-Aboriginal people. This paper discusses some of the ways Aboriginal youth in Toronto understand HIV/AIDS risk and the relevance of their comments for HIV prevention education. This research is part of a larger study conducted with Ontario youth through the Gendering Adolescent AIDS Prevention (GAAP) project.

Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32-33.

Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children and account for a significant proportion of adult nephropathy. The genetic basis of these disorders is not fully understood. We studied seven multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypodysplasia.