Search results for "Heterozygote"

Analysis of the structural integrity of the TAP2 gene in renal cell carcinoma.

2003

The transporter associated with antigen processing (TAP) gene products is involved in the processing of endogenous peptides that bind to MHC class I molecules. Mutations and/or polymorphism within these genes could alter the efficacy of the immune response which might be relevant for the development of autoimmune diseases and cancer. In this study we examined both the structural integrity and the polymorphism of TAP2 in renal cell carcinoma lesions by sequencing TAP2 in renal cell carcinoma lesions and autologous normal kidney epithelium. TAP2 sequence analysis of 31 renal cell carcinoma lesions, one oncocytoma and respective autologous normal kidney epithelium revealed no mutation in the T…

Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

2015

Increasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and within BC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subj…

Gender- and age-related distinctions for the in vivo prooxidant state in Fanconi anaemia patients.

2004

Abstract Some selected oxidative stress parameters were measured in 56 Fanconi anaemia (FA) patients (42 untransplanted and 14 transplanted), 54 FA heterozygotes (parents) and 173 controls. Untransplanted FA patients showed a highly significant increase in leukocyte 8-hydroxy-2’-deoxyguanosine (8-OHdG) (p = 0.00003) and a borderline increase (p = 0.076) in urinary levels of 8-OHdG vs. child controls. These increases were more pronounced in female FA patients (p = 0.00005 for leukocyte 8-OHdG, and p = 0.021 for urinary 8-OHdG). Female FA patients also displayed a highly significant excess of spontaneous chromosomal breaks vs. male patients (p = 0.00026), in the same female:male ratio (≅ 1.4)…

Homozygous disruption of PDZD7 by reciprocal translocation in a consanguineous family: a new member of the Usher syndrome protein interactome causing…

2008

A homozygous reciprocal translocation, 46,XY,t(10;11),t(10;11), was detected in a boy with non-syndromic congenital sensorineural hearing impairment. Both parents and their four other children were heterozygous translocation carriers, 46,XX,t(10;11) and 46,XY,t(10;11), respectively. Fluorescence in situ hybridization of region-specific clones to patient chromosomes was used to localize the breakpoints within bacterial artificial chromosome (BAC) RP11-108L7 on chromosome 10q24.3 and within BAC CTD-2527F12 on chromosome 11q23.3. Junction fragments were cloned by vector ligation and sequenced. The chromosome 10 breakpoint was identified within the PDZ domain containing 7 (PDZD7) gene, disrupti…

A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review

2021

Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y49…

Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwide.

2013

The C9ORF72 Spanish Study Group, et al.

Presence of calreticulin mutations in JAK2-negative polycythemia vera

2014

Abstract Calreticulin (CALR) mutations have recently been reported in JAK2- and MPL-negative Myeloproliferative Neoplasms (MPN), particularly essential thrombocythemia (ET) and primary myelofibrosis (PMF).The clinical course of sporadic CALR-mutated patients seems to be more indolent than that of JAK2-mutated patients. In contrast, no CALR mutation has been found in the 647 published cases of Polycythemia Vera (PV) patients tested. Consequently, CALR mutations were considered exclusive to JAK2 and MPL mutations. Since 98% of PV patients harbor a JAK2 mutation (mostly the V617F mutation in exon 14 and more rarely, in exon 12), the absence of CALR mutations in PV seemed logical. Here, we desc…

Heterogeneity in the genetic basis of human complement C9 deficiency

1998

A novel mutation of gene CBFA1/RUNX2 in cleidocranial dysplasia.

2007

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells into osteoblasts and is essential for membranous as well as endochondral bone formation. In this study of a 14-yr-old boy with typical CCD phenotype, the authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segment…

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

2019

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved resid…