International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.
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):671-9. doi: 10.-010-1036-3. Epub
2010 Jul 22.International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.1, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .1Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, Porto , Portugal.AbstractThe c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156_157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156_157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.PMID:
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External link. Please review our .Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.
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2010 Mar 9;74(10):798-806. doi: 10.1212/WNL.0b013e. Epub
2010 Feb 17.Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.1, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .1Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 88046 Lamezia Terme (CZ), Italy. bruni@arn.itAbstractOBJECTIVE: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide.METHODS: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies.RESULTS: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction.CONCLUSIONS: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature.Comment inPMID:
[PubMed - indexed for MEDLINE] PMCID: PMC3672006 Figure 1 PedigreeExtended pedigree representing known affected subjects of all families with Met146Leu mutation and magnification of Naples family pedigree. E = PH = patients hospitalized in psychiatric hospital.Neurology. 2010 March 9;74(10):798-806.Figure 2 Neuropathology(A–F) Neuropathologic changes were represented by parenchymal Aβ deposits (A, D, F, inferior olive: anti-Aβ42 antibody), neurofibrillary tangles and neuropil threads (B, E, putamen: AT8 antibody), congophilic angiopathy (C, temporal cortex, anti–Aβ40 antibody). (G–H) Immunohistochemical staining showing Tau immunoreactivity in the brain of patients 1768 (G, cortex: RD3 antibody) and 1772 (H, cortex: RD4 antibody). (I) Sarcosyl-insoluble tau from parietal (lane 1), temporal (lane 2), and frontal (lane 3) cortex of the patient appears as 3 major bands at 72, 68, and 64 kDa and a minor band at 60 kDa after immunoblotting with antiserum BR133. Sarcosyl-insoluble tau from AD brain is shown as comparison (lane 4). The human recombinant Tau is reported as marker (lane 5). Bar in A = 25 μm, same magnification in A, B, D, E, and F. Bar in C = 50 μm. Bar in G, H = 30 μm.Neurology. 2010 March 9;74(10):798-806.Figure 3 ImagingAxial slices of [18F]FDG-PET scans of control (C) (male, 38 years) and patient (P). Images were normalized in the Montreal Neurological Institute (MNI) space using SPM2 (Wellcome Department of Imaging Neuroscience, London, UK). The images show relative tracer distribution. Compared to control, the patient shows a clear severe metabolic deficit in the temporoparietal, superior parietal, and posterior cingulate cortices. Slight hypometabolism is evident in the mesial temporal and prefrontal cortex. C: Results of SPM analysis highlight the location of hypometabolic deficit in our patient as compared to controls (p & 0.02 uncorrected) (patients vs 14 healthy controls, age range of controls: 27–70, age was considered in the statistical model of SPM as nuisance covariate).Neurology. 2010 March 9;74(10):798-806.Publication TypesMeSH TermsSubstancesGrant SupportFull Text SourcesOther Literature SourcesMedicalMolecular Biology DatabasesMiscellaneous
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External link. Please review our .founder mutation的用法和样例：
Our discovery of the hemochromatosis founder mutation immediately led to several questions, including, Who was this founder? When and where did this person live?
在发现血色素沉著症的创始者突变后，我们很快想到其他许多问题：这名创始者是谁？他生活在何时何地？
They can pass on the gene to their children and have no symptoms of disease themselves, and the single copy of the founder mutation gives the carrier an advantage in the struggle for survival.
携带者能将突变基因遗传给他们的孩子，本人却不会表现出任何疾病症状，但是这一个创始者突变基因，却可以让他们在遇到困境时拥有生存优势。
Most founder mutations are recessive: only a person with two copies of the affected gene, one from each parent, will suffer from the disease.
大部份创始者突变都是隐性基因，也就是说只有当个体中来自父母的两份基因都有缺陷时才会发病。
Mohammed was the founder of the Muslim religion.
穆罕默德是伊斯兰教的创始人。
founder mutation的海词问答与网友补充：
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