Search results for "Genetic Testing"

Interest of exome sequencing trio-like strategy based on pooled parental DNA for diagnosis and translational research in rare diseases.

2021

Abstract Background Exome sequencing (ES) has become the most powerful and cost‐effective molecular tool for deciphering rare diseases with a diagnostic yield approaching 30%–40% in solo‐ES and 50% in trio‐ES. We applied an innovative parental DNA pooling method to reduce the parental sequencing cost while maintaining the diagnostic yield of trio‐ES. Methods We pooled six (Agilent‐CRE‐v2–100X) or five parental DNA (TWIST‐HCE–70X) aiming to detect allelic balance around 8–10% for heterozygous status. The strategies were applied as second‐tier (74 individuals after negative solo‐ES) and first‐tier approaches (324 individuals without previous ES). Results The allelic balance of parental‐pool v…

Identification of a genetic contamination in a commercial mouse strain using two panels of polymorphic markers

2007

Rapid detection of genetic contamination is critical in mouse studies involving inbred strains. During a Quantitative Trait Locus (QTL) study using simple sequence length polymorphism (SSLP) markers, we noticed heterozygosity at some loci of a commercially available inbred C57BL/6N mouse strain, suggesting a contamination by another mouse strain. A panel of 100 single-nucleotide polymorphism (SNP) markers was used to confirm and specify the genetic contamination suspected. Retrospective analyses demonstrated that the contamination took place as early as autumn 2003 and has persisted ever since at a fairly constant level. Contaminating alleles most probably originated from a DBA strain. Our…

Late onset and pregnancy-induced congenital thrombotic thrombocytopenic purpura

2014

SummaryWe report on our patient (case 2) who experienced a first acute episode of thrombotic thrombocytopenic purpura (TTP) at the age of 19 years during her first pregnancy in 1976 which ended in a spontaneous abortion in the 30th gestational week. Treatment with red blood cell concentrates was implemented and splenectomy was performed. After having suffered from several TTP episodes in 1977, possibly mitigated by acetylsalicylic acid therapy, an interruption and sterilization were performed in 1980 in her second pregnancy thereby avoiding another disease flare-up. Her elder sister (case 1) had been diagnosed with TTP in 1974, also during her first pregnancy. She died in 1977 during her se…

Founder mutations in BRCA1 and BRCA2 genes

2007

BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive f…

Involvement of large rearrangements in MSH6 and PMS2 genes in southern Italian patients with lynch syndrome

2018

Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes. Most of germline mutations are point variants, followed by large rearrangements that account to 15-55% of all pathogenic mutations. Many study reporting the frequency of large rearrangements in the MLH1 and MSH2 genes were performed, while, little is known about the contribution of large rearrangements in other MMR genes, as PMS2 and MSH6. Therefore, in this study we investigated the involvment of large rearrangements in MSH6 and PMS2 genes in a well-characterized series of 20 LS southern Italian patients. Methods: These large rearrangements are not usuall…

Who has to undergo cancer genetic testing? A perspective

2017

Genetic testing is a medical tool employed to screen changes in genes linked to cancer and other genetic diseases. Genetic tests are available for breast, ovarian, colon, thyroid, and some other cancers and they represent the main tool for early identification of the “risk” subjects. The choice to undergo genetic testing by a healthy or affected cancer patient with family history of the cancer has to be the fruit of a careful and prudent assessment of the advantages and disadvantages discussed during oncogenetic counselling. The latter, in turn, in the case of a patient’s positive and informed choice, must constantly affiliate the genetic testing, in order to preserve the prediction and inf…

Addressing the gap between genetics knowledge and clinical practice: a pilot study to implement genetics education among physicians in Italy

2012

As a result of large investments in basic science, the genomic discoveries have brought outstanding advances in understanding the molecular basis of human health. Hundreds of genes whose variations contribute to human diseases, or patients’ responses to drug treatments or even to vaccination have been discovered, laying the foundation for a paradigm shift in healthcare...

A novel nonsense mutation in exon 2 of the factor IX gene resulting in severe haemophilia B

2006

The von Hippel-Lindau tumor suppressor gene

1997

Abstract The von Hippel-Lindau (VHL) disease is an inherited tumor susceptibility syndrome featuring a high variety of benign and malignant tumors. The gene has been localized and cloned at 3p25-26. Recent functional analysis defined the VHL gene product as an inhibitor of the transcription elongation process. Its possible involvement in the vascularization process may explain the histologic features of VHL tumors providing insight into basic mechanism of tumorigenesis. Direct genetic testing is available for patients affected with VHL. Seventy to eighty percent of the germline mutations expected could be detected. As first geno/phenotype correlations have been established, we are now begin…

Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?

2006

Abstract Background: Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies. Methods: Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences). Results: We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60…