Genetic Service

Trieste, Italy

Genetic Service

Trieste, Italy
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Brandao L.C.,Federal University of Pernambuco | Vatta S.,Laboratory of Immunopathology | Guimaraes R.,Federal University of Pernambuco | Segat L.,Federal University of Pernambuco | And 6 more authors.
Human Immunology | Year: 2010

The aim of this study was to identify in the Brazilian population the frequency of human leukocyte antigen (HLA) DQ2.5 and DQ8 haplotypes conferring risk for type 1 diabetes (T1D), and to validate a new genotyping method aimed at cost reduction and automation. A total of 184 children and adolescents with T1D and 184 healthy individuals from Recife (northeastern Brazil) were analyzed using the conventional polymerase chain reaction-sequence-specific primers HLA genotyping and a newly described Tag-single-nucleotide polymorphism real-time polymerase chain reaction. The Tag-single-nucleotide polymorphism-based HLA genotyping method was successfully validated, proved to be robust, with limited cost and thus could be successfully used for the identification of genetic susceptibility for T1D in areas with limited financial resources. Our findings report for the first time the distribution of DQ2.5 and DQ8 HLA risk haplotypes associated with T1D in northeastern Brazil and evidence a major risk for developing T1D when the heterozygous DQ2.5/DQ8 or the homozygous DQ2.5/DQ2.5 haplotypes are present. © 2010 American Society for Histocompatibility and Immunogenetics.


Fabris A.,Genetic Service | Segat L.,Genetic Service | Segat L.,Federal University of Pernambuco | Catamo E.,Genetic Service | And 4 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: Nonclassical major histocompatibility class I HLA-G antigen is a tolerogenic molecule that inhibits lytic activity of natural killer (NK) cells and cytotoxic T lymphocytes. Because of its immunomodulatory and tolerogenic properties, HLA-G molecules may have a role in celiac disease (CD). We analyzed the HLA-G 14 bp deletion/insertion polymorphism, known to have a functional effect on mRNA stability, in a group of 522 CD patients, stratified for the presence of HLA-DQ2 genotype, and 400 healthy individuals to evaluate the possible effect of the polymorphism on the risk to develop the disease. Methods: HLA-G 14 bp deletion/insertion polymorphism (rs1704) was detected by polymerase chain reaction and double-checked by direct sequencing. Results: The 14bp inserted (I) allele and the homozygous I/I genotype were significantly more frequent in CD patients than in healthy controls. The presence of I allele was associated with an increased risk of CD (OR 1.35) and the effect of I allele was consistent with a recessive genetic model (P<0.001). Conclusions: Our results also indicate that the effect of the HLA-G D/I polymorphism is restricted for HLA-DQ2, and not simply due to the presence of linkage disequilibrium with the major known risk factor; moreover we found that the presence of the I allele confers an increased risk of CD in addition to the risk conferred by HLA-DQ2 alone and that subjects that carry both DQ2 and HLA-G I alleles have an increased risk of CD than subjects that carry DQ2 but not the I allele. © 2011 by the American College of Gastroenterology.


Sandrin-Garcia P.,Federal University of Pernambuco | Brandao L.A.C.,Federal University of Pernambuco | Coelho A.V.C.,Federal University of Pernambuco | Guimaraes R.L.,Federal University of Pernambuco | And 5 more authors.
Human Immunology | Year: 2011

Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the O allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations. © 2011 American Society for Histocompatibility and Immunogenetics.


Canueto J.,Molecular Medicine Unit | Canueto J.,University of Salamanca | Canueto J.,Hospital Nuestra Senora Of Sonsoles | Giros M.,Hospital Clinic Barcelona | And 21 more authors.
British Journal of Dermatology | Year: 2012

Background Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholestenol and 8-dehydrocholesterol. Objectives To expand the understanding of CDPX2, clinically, biochemically and genetically. Methods We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. Results In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. Conclusions No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.


Huber C.,University of Paris Descartes | Fradin M.,University of Paris Descartes | Edouard T.,Hospital Purpan | Le Merrer M.,University of Paris Descartes | And 15 more authors.
Human Mutation | Year: 2010

3-M syndrome is an autosomal recessive disorder characterized by severe pre- and postnatal growth retardation and minor skeletal changes. We have previously identified CUL7 as a disease-causing gene but we have also provided evidence of genetic heterogeneity in the 3-M syndrome. By homozygosity mapping in two inbred families, we found a second disease locus on chromosome 2q35-36.1 in a 5.2-Mb interval that encompasses 60 genes. To select candidate genes, we performed microarray analysis of cultured skin fibroblast RNA from one patient, looking for genes with altered expression; we found decreased expression of IGFBP2 and increased expression of IGFBP5. However, direct sequencing of these two genes failed to detect any anomaly. We then considered other candidate genes by their function/location and found nine distinct mutations in the OBSL1 gene in 13 families including eight nonsense and one missense mutations. To further understand the links between OBSL1, CUL7, and insulin-like growth factor binding proteins (IGFBPs), we performed real-time quantitative PCR (RT-PCR) analysis for OBSL1, CUL7, IGFBP2, and IGFBP5, using cultured fibroblast RNAs from two patients with distinct OBSL1 mutations (p.F697G; p.H814RfsX15). We found normal CUL7 mRNA levels but abnormal IGFBP2 and IGFBP5 mRNA levels in the two patients, suggesting that OBSL1 modulates the expression of IGFBP proteins. © 2009 Wiley-Liss, Inc.


Comar M.,University of Trieste | Segat L.,Genetic Service | Crovella S.,Genetic Service | Bovenzi M.,University of Trieste | And 2 more authors.
Human Immunology | Year: 2011

The simultaneous detection of oncogenic human papillomavirus (HPV) and BK virus (BKV) has been recently reported in cervical cancers, suggesting that these viruses may act together in the process of cell transformation; host genetic polymorphisms may also influence virus persistence/reactivation. To disclose a possible role of the gene encoding for the mannose-binding lectin, MBL2, in susceptibility to BKV infection, we analyzed functional polymorphisms in the first exon of MBL2 in women stratified for the presence/absence of BKV and affected by different grades of HPV-induced cervical precancerous lesions. All BKV-positive samples were also HPV positive (HPV 16), and all presented with high-grade squamous intraepithelial lesions. The MBL2 A allele was significantly more frequent in BKV-negative patients than in BKV-positive patients. These data indicate a possible role for the A allele in conferring protection to BKV infection in high-risk HPV-positive women (odds ratio 0.40, 95% confidence interval 0.20-0.85, p = 0.01). © 2011 American Society for Histocompatibility and Immunogenetics.


Hopper B.,Genetic Service | Buckman M.,Genetic Service | Edwards M.,Hunter Genetics
Twin Research and Human Genetics | Year: 2011

Telegenetics is a new development in the service delivery of Genetic Services in Australia. This project was designed to establish if it was an acceptable alternative to a face-to-face consultation in the genetic assessment of intellectual disability, including morphological assessment, of the patient. Ten children from two outreach clinics in rural NSW who were referred by their pediatrician were assessed by a single geneticist via telehealth and then seen again face-to-face as a 'gold standard'. Satisfaction surveys were then sent to both the parents and the referring pediatricians. After the face-to-face appointment, the clinical geneticist reviewed the recordings of both the transmitted footage and the high definition footage that was sent separately. There were very few morphological findings missed by the telegenetic assessments. The discrepancies that were noted could decrease in frequency as staff become more familiar with the methods. The parents of the patients reported no problem with the cameras and telehealth. They would have preferred face-to-face appointment but would be happy to have the telehealth appointment if it meant being seen earlier. This pilot study suggests that clinical genetic diagnostic assessment could be performed by telemedicine.


Segat L.,Genetic Service | Morgutti M.,Genetic Service | Athanasakis E.,Genetic Service | Trevisiol C.,San Polo Hospital | And 3 more authors.
International Journal of Immunogenetics | Year: 2010

Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5'- untranslated region of the DEFB1 gene (namely g- 52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g- 20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients. © 2010 Blackwell Publishing Ltd.


PubMed | Genetic Service
Type: Comparative Study | Journal: The American journal of gastroenterology | Year: 2011

Nonclassical major histocompatibility class I HLA-G antigen is a tolerogenic molecule that inhibits lytic activity of natural killer (NK) cells and cytotoxic T lymphocytes. Because of its immunomodulatory and tolerogenic properties, HLA-G molecules may have a role in celiac disease (CD). We analyzed the HLA-G 14 bp deletion/insertion polymorphism, known to have a functional effect on mRNA stability, in a group of 522 CD patients, stratified for the presence of HLA-DQ2 genotype, and 400 healthy individuals to evaluate the possible effect of the polymorphism on the risk to develop the disease.HLA-G 14 bp deletion/insertion polymorphism (rs1704) was detected by polymerase chain reaction and double-checked by direct sequencing.The 14 bp inserted (I) allele and the homozygous I/I genotype were significantly more frequent in CD patients than in healthy controls. The presence of I allele was associated with an increased risk of CD (OR 1.35) and the effect of I allele was consistent with a recessive genetic model (P<0.001).Our results also indicate that the effect of the HLA-G D/I polymorphism is restricted for HLA-DQ2, and not simply due to the presence of linkage disequilibrium with the major known risk factor; moreover we found that the presence of the I allele confers an increased risk of CD in addition to the risk conferred by HLA-DQ2 alone and that subjects that carry both DQ2 and HLA-G I alleles have an increased risk of CD than subjects that carry DQ2 but not the I allele.


PubMed | Genetic Service
Type: Evaluation Studies | Journal: Twin research and human genetics : the official journal of the International Society for Twin Studies | Year: 2011

Telegenetics is a new development in the service delivery of Genetic Services in Australia. This project was designed to establish if it was an acceptable alternative to a face-to-face consultation in the genetic assessment of intellectual disability, including morphological assessment, of the patient. Ten children from two outreach clinics in rural NSW who were referred by their pediatrician were assessed by a single geneticist via telehealth and then seen again face-to-face as a gold standard. Satisfaction surveys were then sent to both the parents and the referring pediatricians. After the face-to-face appointment, the clinical geneticist reviewed the recordings of both the transmitted footage and the high definition footage that was sent separately. There were very few morphological findings missed by the telegenetic assessments. The discrepancies that were noted could decrease in frequency as staff become more familiar with the methods. The parents of the patients reported no problem with the cameras and telehealth. They would have preferred face-to-face appointment but would be happy to have the telehealth appointment if it meant being seen earlier. This pilot study suggests that clinical genetic diagnostic assessment could be performed by telemedicine.

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