Search results for "Genetic algorithm"
showing 10 items of 834 documents
Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia
2006
Skeletal dysplasias are difficult to diagnose for the nonexpert. In a previous study of patients with multiple epiphyseal dysplasia (MED), we identified cartilage oligomeric matrix protein (COMP) mutations in only 36% of cases and suspected that the low-mutation detection rate was partially due to misdiagnosis. We therefore instituted a clinical–radiographic review system, whereby all cases were evaluated by a panel of skeletal dysplasia experts (European Skeletal Dysplasia Network). Only those patients in whom the diagnosis of MED was confirmed by the panel were screened for mutations. Under this regimen the mutation detection rate increased to 81%. When clinical–radiological diagnostic cr…
Treatment of Metachronous and Simultaneous Liver Metastases of Pancreatic Cancer
2009
<i>Aim:</i> Patients were analyzed who underwent treatment of liver metastases from pancreatic cancer. <i>Methods:</i> Selection criteria were the possibility of R0 resection of the primary and/or the liver metastases, no other sites of metastases, and the presentation of liver metastases. A comparison of treatment by surgery versus chemotherapy regarding overall survival and disease-free interval was performed. <i>Results:</i> Between 1996 and 2008, a total number of 23 patients were retrospectively identified from a prospective database of 193 cases of pancreatic cancer. In 14 cases, liver metastases were found simultaneously, and in 9 cases metachronou…
High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability.
2007
Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has been greatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence gene rearrangements not detectable by standard screening methods. However, no criteria for selection of cases to be submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection of familial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2 conventional mutation screening. One hundred and seventy-seven probands were investigated for germline BRCA1/2 mutations after assessment of genetic risk using BRCAPro. Proban…
Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W.
2003
Multiple epiphyseal dysplasia (MED) is a generalised skeletal dysplasia that although relatively mild is associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. In the past, the disorder was subdivided into the milder Ribbing type, usually with flattened epiphyses,1 and the more severe Fairbank type with round epiphyses,2 but many cases were not classifiable as clearly either type.3 MED can be caused by mutations in at least six separate genes: COMP ,4–7 collagen IX ( COL9A1 , COL9A2 , and COL9A3 ),8–13 matrilin 3 ( MATN3 ),15 and the sulphate transporter, DTDST ( DTDST/SLC26A2 ). We have previously repor…
Whole-exome sequencing identifies the first French MODY 6 family with a new mutation in the NEUROD1 gene
2020
Abstract Aim The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES). Methods WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing. Results In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the sa…
Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene
2003
Abstract We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvemen…
A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer
2005
A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother's proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband's brother and her two sons. Direct automatic sequen…
BRAFV600E Mutation and p27kip1 Expression in Papillary Carcinomas of the Thyroid ≤1 cm and Their Paired Lymph Node Metastases
2007
BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E …
Fine-Needle Aspiration (FNAB) Molecular Analysis for the Diagnosis of Papillary Thyroid Carcinoma through BRAFv600E mutation and RET/PTC rearrangement
2007
Objective: To evaluate BRAFV600E mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB’s usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET=PTC1 and RET=PTC3 rearrangements obtained from ex vivo thyroid nodules. Design: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET=PTC rearrangements. The results were compared with the cytological diagnosis and histopathol…
The role of CARD15 mutations and smoking in the course of Crohn's disease in a Mediterranean area.
2008
To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.A total of 110 patients were operated on and 32 were reoperated on. The …