Silva N.,Hospital Braga |
Costa M.,Hospital Braga |
Silva A.,Hospital Braga |
Sa C.,Hospital Braga |
And 5 more authors.
Endocrinologia y Nutricion | Year: 2013
We report a neonatal case of systemic pseudohypoaldosteronism type 1 caused by a novel mutation in the SCNN1A gene (homozygous c.1052. +. 2dupT in intron 3) in which the patient presented with life-threatening hyperkalemia, hyponatremia and metabolic acidosis. It remains uncertain if there is genotype-phenotype correlation, due to the rarity of the disease. This mutation, which to our best knowledge has not been described before, was associated with a very severe phenotype requiring aggressive therapy. © 2012 SEEN. Source
Barber J.C.K.,University of Southampton |
Rodrigues R.,GDPN |
Maloney V.K.,Wessex Regional Genetics Laboratory |
Taborda F.,Centro Hospitalar do Porto |
And 2 more authors.
Cytogenetic and Genome Research | Year: 2013
Microscopically visible copy number variations within the proximal short arm heterochromatin and proximal long arm of chromosome 9 have been described as euchromatic variants (EVs) and are derived from extensive segmental duplications (SDs) that map to both the proximal short and long arms of chromosome 9. Recently, 3-4 additional copies of an SD cassette were found in 2 families with duplication EVs of 9q13-q21. Here, we report a third family with a duplication EV of 9q13-q21.1 that was ascertained at prenatal diagnosis for advanced maternal age and found in the fetus and her phenotypically normal mother. Dual-colour fluorescence in situ hybridization with bacterial artificial chromosomes RP11-246P17 and RP11-211E19 was consistent with the EV chromosome having 1-2 additional copies of a similar SD cassette, except that the SD-boundary clone RP11-88I18 was not apparently included. It is important to distinguish the 9q13-q21.1 EVs from possible pathogenic imbalances of chromosome 9, especially at prenatal diagnosis, as these EVs have no established phenotypic or reproductive consequences. The nature of the G-dark bands in 9q13-q21 EVs is briefly discussed. Copyright © 2013 S. Karger AG, Basel. Source
Leite M.,University of Porto |
Corso G.,University of Porto |
Corso G.,University of Siena |
Corso G.,Institute of Tumours of Tuscany ITT |
And 12 more authors.
International Journal of Cancer | Year: 2011
Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis occurring in 20% of gastric cancer (GC). However, it is not clear whether MSI phenotype preferentially occurs in the sporadic or familial GC, when stringent inclusion criteria are used. The aim of this study was to compare the frequency of MSI and hypermethylation of MLH1 promoter in a large series of familial GC patients (non-HNPCC and non-CDH1-related) and sporadic cases. Additionally, we analysed the immunoexpression of MMR proteins in a fraction of cases. Overall, the frequency of familial GC was 7.1%, and the frequency of hereditary tumours was 4.6%. MSI phenotype and MLH1 hypermethylation frequencies were not statistical different between familial and sporadic GC settings. Further, the MSI phenotype was not associated with any clinico-pathological features studied in the familial GC setting, whereas in the sporadic setting, it was associated with older age, female gender and intestinal histotype. Using our stringent Amsterdam-based clinical criteria to select familial GC (number of cases, age of onset), we verified that sporadic and familial cases differed in gender but shared histopathological features. We verified that the frequency of MSI was similar in familial and sporadic GC settings, demonstrating that this molecular phenotype is not a hallmark of familial GC in contrast to what is verified in HNPCC. Moreover, we observed that the frequency of MLH1 hypermethylation is similar in sporadic and familial cases suggesting that in both settings MSI is not associated to MMR genetic alterations but in contrast to epigenetic deregulation. Copyright © 2010 UICC. Source
Barber J.C.,Wessex Regional Genetics Laboratory |
Barber J.C.,National Genetics Reference Laboratory Wessex |
Barber J.C.,University of Southampton |
Bunyan D.,Wessex Regional Genetics Laboratory |
And 12 more authors.
Molecular Cytogenetics | Year: 2010
Background: The 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis. Methods. Additional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH). Results. Three cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome. Conclusions. Our data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity. © 2010 Barber et al; licensee BioMed Central Ltd. Source