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Bruno Dallapiccola - One of the best experts on this subject based on the ideXlab platform.

  • the search for Hemizygosity at 22qll in patients with isolated cleft palate
    Journal of Craniofacial Genetics and Developmental Biology, 1996
    Co-Authors: Rita Mingarelli, Aldo Giannotti, Maria Cristina Digilio, Francesca Amati, Aldo Mari, Giuseppe Novelli, Lucio Standoli, Bruno Dallapiccola
    Abstract:

    : The striking association between oral clefting and the velocardio-facial syndrome (VCFS), a common disorder pathogenetically related to 22q11 deficiency, has prompted the search for this deletion in a group of patients with isolated cleft palate. (CP). Thirty-three patients with posterior CP and 5 with complete CP were included in this study, together with 12 patients with a clinical diagnosis of VCFS. Standard and high resolution chromosome analysis was performed, providing normal results. Southern blotting followed by densitometric analysis and fluorescent in situ hydridization of region 22q11 showed no single case of deletion among the isolated CP patients, while deficiency was found in 10 of 12 VCFS patients. These results demonstrate that Hemizygosity at 22q11 is not increased in isolated CP.

  • 22q11 deletions in isolated and syndromic patients with tetralogy of Fallot
    Human Genetics, 1995
    Co-Authors: Francesca Amati, Aldo Giannotti, Maria Cristina Digilio, Bruno Marino, Rita Mingarelli, Aldo Mari, Giuseppe Novelli, Bruno Dallapiccola
    Abstract:

    Tetralogy of Fallot (TF) is a congenital conotruncal heart defect commonly found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. The deletion of chromosome 22q11 (de122q11) is a well established cause of DGS and VCFS, and it has been demonstrated also in sporadic or familial cases of TF. In order to investigate the prevalence of de122q11 in patients with TF, we analyzed the DNA of 137 consecutive patients with syndromic and isolated TF, using the HD7k probe, which detects Hemizygosity for the D22S134 locus. De122q11 has been detected in 11/26 (42%) syndromic patients. Evidence for Hemizygosity was obtained in all patients with DGS and in 8/15 patients with VCFS. None of the 107 patients with isolated TF had de122q11. Our experience suggests that children with TF and de122q11 always present major or minor extracardiac anomalies. These features, including subtle facial dysmorphisms, should be checked routinely in patients with TF and other conotruncal heart defects.

  • Cayler cardiofacial syndrome and del22qll: Part of the CATCH22 phenotype
    American Journal of Medical Genetics, 1994
    Co-Authors: Aldo Giannotti, Maria Cristina Digilio, Bruno Marino, Rita Mingarelli, Bruno Dallapiccola
    Abstract:

    The authors report evidence supporting the hypothesis that del(22)(q11) can be a pathogenetic mechanism for the association between hypoplasia of the depressor anguli oris muscle (DAOM) and conotruncal cardiac malformations. A series of over 180 patients was investigated with deletions of 22q11 with conotruncal defects. About 2/3 of these patients had isolated, nonfamilial cardiac defects. Hemizygosity was searched using the HD7k probe and densitometric analysis. In the patients with molecular evidence of del(22)(q11), Hemizygosity was confirmed also using fluorescence in situ hybridization (FISH) with SC11.1 probe. No deletion was found in the parents of hemizygous patients. 16 refs.

Albert Schinzel - One of the best experts on this subject based on the ideXlab platform.

  • phenotype of the williams beuren syndrome associated with Hemizygosity at the elastin locus
    European Journal of Pediatrics, 1995
    Co-Authors: Dieter Kotzot, F Bernasconi, Lukrecija Brecevic, Wendy P Robinson, P Kiss, Gyorgy Kosztolanyi, Iosif W Lurie, Andrea Supertifurga, Albert Schinzel
    Abstract:

    To correlate presence or absence of a 7q11 microdeletion with the clinical picture of the Williams-Beuren syndrome (WBS), we investigated 29 patients with a clinical diagnosis of WBS or WBS-like features, aged 1–30 years, using molecular analysis and/or fluorescent in situ hybridization (FISH). Deletions at 7q11 were found in 75% of the patients (22 out of 29). Nine deletions occurred on a paternal, and ten on a maternal chromosome; three deletions were demonstrated by FISH only, and parental origin could thus not be determined. All deletion patients aged between 2 years and puberty displayed a distinct pattern of facial features (including periorbital fullness, short nose with flat bridge, wide mouth, and full lips and cheeks), the characteristic outgoing social behaviour, as well as moderate growth and mental retardation. Twothirds (15 out of 22) had a cardiovascular malformation, but only one third (7 of 22) had supravalvular aortic stenosis (SVAS). A stellate iris pattern was also present in one-third of the patients only. In the four adult patients with 7q11 deletions, there was prominence of the lower lip whereas fullness of cheeks and periorbital tissue was not seen.

Andrew G Mccubbin - One of the best experts on this subject based on the ideXlab platform.

  • the long and short of the s locus in turnera passifloraceae
    New Phytologist, 2019
    Co-Authors: Joel S Shore, Hasan J Hamam, Paul D J Chafe, Jonathan D J Labonne, Paige M Henning, Andrew G Mccubbin
    Abstract:

    Distyly is an intriguing floral adaptation that increases pollen transfer precision and restricts inbreeding. It has been a model system in evolutionary biology since Darwin. Although the S-locus determines the long- and short-styled morphs, the genes were unknown in Turnera. We have now identified these genes. We used deletion mapping to identify, and then sequence, BAC clones and genome scaffolds to construct S/s haplotypes. We investigated candidate gene expression, Hemizygosity, and used mutants, to explore gene function. The s-haplotype possessed 21 genes collinear with a region of chromosome 7 of grape. The S-haplotype possessed three additional genes and two inversions. TsSPH1 was expressed in filaments and anthers, TsYUC6 in anthers and TsBAHD in pistils. Long-homostyle mutants did not possess TsBAHD and a short-homostyle mutant did not express TsSPH1. Three hemizygous genes appear to determine S-morph characteristics in T. subulata. Hemizygosity is common to all distylous species investigated, yet the genes differ. The pistil candidate gene, TsBAHD, differs from that of Primula, but both may inactivate brassinosteroids causing short styles. TsYUC6 is involved in auxin synthesis and likely determines pollen characteristics. TsSPH1 is likely involved in filament elongation. We propose an incompatibility mechanism involving TsYUC6 and TsBAHD.

  • The long and short of the S‐locus in Turnera (Passifloraceae)
    New Phytologist, 2019
    Co-Authors: Joel S Shore, Hasan J Hamam, Paul D J Chafe, Jonathan D J Labonne, Paige M Henning, Andrew G Mccubbin
    Abstract:

    Distyly is an intriguing floral adaptation that increases pollen transfer precision and restricts inbreeding. It has been a model system in evolutionary biology since Darwin. Although the S-locus determines the long- and short-styled morphs, the genes were unknown in Turnera. We have now identified these genes. We used deletion mapping to identify, and then sequence, BAC clones and genome scaffolds to construct S/s haplotypes. We investigated candidate gene expression, Hemizygosity, and used mutants, to explore gene function. The s-haplotype possessed 21 genes collinear with a region of chromosome 7 of grape. The S-haplotype possessed three additional genes and two inversions. TsSPH1 was expressed in filaments and anthers, TsYUC6 in anthers and TsBAHD in pistils. Long-homostyle mutants did not possess TsBAHD and a short-homostyle mutant did not express TsSPH1. Three hemizygous genes appear to determine S-morph characteristics in T. subulata. Hemizygosity is common to all distylous species investigated, yet the genes differ. The pistil candidate gene, TsBAHD, differs from that of Primula, but both may inactivate brassinosteroids causing short styles. TsYUC6 is involved in auxin synthesis and likely determines pollen characteristics. TsSPH1 is likely involved in filament elongation. We propose an incompatibility mechanism involving TsYUC6 and TsBAHD.

Luis Perez A Jurado - One of the best experts on this subject based on the ideXlab platform.

  • Hemizygosity at the ncf1 gene in patients with williams beuren syndrome decreases their risk of hypertension
    American Journal of Human Genetics, 2006
    Co-Authors: Miguel Del Campo, Anna Antonell, Luis F Magano, Francisco J Munoz, Raquel Flores, Monica Bayes, Luis Perez A Jurado
    Abstract:

    Williams-Beuren syndrome (WBS), caused by a heterozygous deletion at 7q11.23, represents a model for studying hypertension, the leading risk factor for mortality worldwide, in a genetically determined disorder. Haploinsufficiency at the elastin gene is known to lead to the vascular stenoses in WBS and is also thought to predispose to hypertension, present in ∼50% of patients. Detailed clinical and molecular characterization of 96 patients with WBS was performed to explore clinical-molecular correlations. Deletion breakpoints were precisely defined and were found to result in variability at two genes, NCF1 and GTF2IRD2. Hypertension was significantly less prevalent in patients with WBS who had the deletion that included NCF1 (P=.02), a gene coding for the p47phox subunit of the NADPH oxidase. Decreased p47phox protein levels, decreased superoxide anion production, and lower protein nitrotyrosination were all observed in cell lines from patients hemizygous at NCF1. Our results indicate that the loss of a functional copy of NCF1 protects a proportion of patients with WBS against hypertension, likely through a lifelong reduced angiotensin II–mediated oxidative stress. Therefore, antioxidant therapy that reduces NADPH oxidase activity might have a potential benefit in identifiable patients with WBS in whom serious complications related to hypertension have been reported, as well as in forms of essential hypertension mediated by a similar pathogenic mechanism.

Marco Giovannini - One of the best experts on this subject based on the ideXlab platform.

  • Synergy of Nf2 and p53 mutations in development of malignant tumours of neural crest origin
    Oncogene, 2004
    Co-Authors: Els Robanus-maandag, Marco Giovannini, Martin Van Der Valk, Michiko Niwa-kawakita, Vincent Abramowski, Cristina Antonescu, Gilles Thomas, Anton Berns
    Abstract:

    Previously, we have mimicked human neurofibromatosis type 2 (NF2) in conditional Nf2 mutant (P0 Cre ; Nf2 ^flox2/flox2) mice. Schwannomas, characteristic for NF2, were found at low frequency in older mice. Here, we report that these mice, upon additional Hemizygosity for p53 , rapidly develop multiple tumours showing features consistent with malignant peripheral nerve sheath tumours. Thus, p53 Hemizygosity promotes tumorigenesis of mutant Nf2 peripheral nerve cells. In contrast, young P0 Cre ; Nf2 ^flox2/+; p53 ^+/− cis mice mainly succumb to Nf2/p53 -related osteogenic tumours. Therefore, Cre-mediated early biallelic loss of Nf2 function in neural crest-derived cells hemizygous for p53 results in resistance to osteogenic tumours and increased susceptibility to peripheral nerve sheath tumours.

  • Hemizygosity of nf2 is associated with increased susceptibility to asbestos induced peritoneal tumours
    Oncogene, 2003
    Co-Authors: Jocelyne Fleuryfeith, Marco Giovannini, Vincent Abramowski, Céline Lecomte, Annie Renier, Mireille Matrat, Laurence Kheuang, Françoise Levy, Anne Janin, Marie-claude Jaurand
    Abstract:

    Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 Hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2KO3/+), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2KO3/+ mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2KO3/+ mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.

  • Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours.
    Oncogene, 2003
    Co-Authors: Jocelyne Fleury-feith, Marco Giovannini, Vincent Abramowski, Céline Lecomte, Annie Renier, Mireille Matrat, Laurence Kheuang, Françoise Levy, Anne Janin, Marie-claude Jaurand
    Abstract:

    Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 Hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2KO3/+), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2KO3/+ mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P

  • Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse
    Genes & Development, 2002
    Co-Authors: Michel Kalamarides, Michiko Niwa-kawakita, Vincent Abramowski, Gilles Thomas, Anne Janin, Hélène Leblois, Michel Perricaudet, David H. Gutmann, Marco Giovannini
    Abstract:

    Biallelic NF2 gene inactivation is common in sporadic and in neurofibromatosis type 2 (NF2)-related meningiomas. We show that, beginning at four months of age, thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2 developed a range of meningioma subtypes histologically similar to the human tumors. Additional Hemizygosity for p53 did not modify meningioma frequency or progression suggesting that Nf2 and p53 mutations do not synergize in meningeal tumorigenesis. This first mouse model initiated with a genetic lesion found in human meningiomas provides a powerful tool for investigating tumor progression and for the preclinical evaluation of therapeutic interventions.