Distal Xq28 region: Analysis of two peculiar cases of Incontinentia Pigmenti (IP) and search for new Genetic Markers. (Abstract/Poster in atti di convegno)

Type
Label
  • Distal Xq28 region: Analysis of two peculiar cases of Incontinentia Pigmenti (IP) and search for new Genetic Markers. (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • M.D'Urso1 , MG Miano1, T. Bardaro1,2 , G. Fimiani1, F. Fusco1, J. Monfregola1, V. Mercadante1, E. Russo2, A. Cevenini1, C. Laperuta1, S. Crispi2, P. De Luca2 , M.V. Ursini1. (2003)
    Distal Xq28 region: Analysis of two peculiar cases of Incontinentia Pigmenti (IP) and search for new Genetic Markers.
    in Human Genome Meeting, HUGO Conference, Cancun, Mexico, April 27-30, 2003
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • M.D'Urso1 , MG Miano1, T. Bardaro1,2 , G. Fimiani1, F. Fusco1, J. Monfregola1, V. Mercadante1, E. Russo2, A. Cevenini1, C. Laperuta1, S. Crispi2, P. De Luca2 , M.V. Ursini1. (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1.Institute of Genetics and Biophysics \"Adriano Buzzati Traverso\" IGB-ABT CNR, Italy; 2.BioGeM Consortium, Italy. (literal)
Titolo
  • Distal Xq28 region: Analysis of two peculiar cases of Incontinentia Pigmenti (IP) and search for new Genetic Markers. (literal)
Abstract
  • The cytogenetic region q28 of the human X chromosome has great health relevance in Medical Genetics because it contains several disease loci. Familial Incontinentia pigmenti (IP, MIM308300) is a rare X-linked dominant disorder of Xq28 which affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO/IKBKG,IKK? (MIM 300248) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMO lead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-?. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second non-functional copy of the gene, ?NEMO, was identified, opposite in direction to NEMO in a 35.5 kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 ?NEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP. Notably, in Xq28 maps several disease loci which causative gene is still unknown, such as X-linked polymicrogyria (PMGX) and a form of non specific X mental retardation (MRX72). The difficulty to isolate new Xq28 disease genes is remarkable because of the paucity of polymorphic markers available for linkage study.Thus, we have initiated a systematic search of new short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) in 1.6 Mb of distal Xq28, between G6PD gene and the telomeric repeat TTAGGG. Starting from the nucleotide sequence, performed in our laboratory, we have selected new microsatellites. Sequence analysis of the genomic clones was performed by CENSOR software looking for DNA repeated elements. Specific primer pairs were designed for each potential STRs and used in QF-PCR reactions. DNA pools from males of 40 CEPH families were genotyped to establish the number of alleles and their frequencies in the Caucasian population. Based on this strategy, we are able to establish the index of heterozigosity and consequently the power of each new Xq28 marker to be used in linkage studies. We found significant evidences of the presence of several new STRs that we are currently using to narrow down the MRX72 locus. Furter study are in progress to construct haplotypes of distal Xq28 to evaluate linkage disiquilibrium. (literal)
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