1. Determination of the Genomic Structure of the XNP/ATRX Gene Encoding a Potential Zinc Finger Helicase
- Author
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Carlos Cardoso, V. Proud, Michel Fontes, Charles E. Schwartz, Pierre Chiaroni, Laurent Villard, Anne-Marie Lossi, Laurence Colleaux, Greenwood Genetic Center [Greenwood, South Carolina, USA], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: Sequence Analysis, DNA ,Transcription, Genetic ,MESH: Introns ,Restriction Mapping ,MESH: DNA Helicases ,MESH: Amino Acid Sequence ,Polymerase Chain Reaction ,Exon ,Coding region ,MESH: Syndrome ,MESH: Restriction Mapping ,Electrophoresis, Agar Gel ,Genetics ,Zinc finger ,0303 health sciences ,Splice site mutation ,MESH: X-linked Nuclear Protein ,MESH: Alternative Splicing ,030305 genetics & heredity ,Nuclear Proteins ,Zinc Fingers ,Exons ,Syndrome ,MESH: alpha-Thalassemia ,Polyglutamic Acid ,RNA splicing ,X-linked Nuclear Protein ,X Chromosome ,MESH: Mutation ,Molecular Sequence Data ,Biology ,MESH: Intellectual Disability ,03 medical and health sciences ,alpha-Thalassemia ,Intellectual Disability ,Humans ,MESH: Zinc Fingers ,Amino Acid Sequence ,RNA, Messenger ,ATRX ,030304 developmental biology ,MESH: RNA, Messenger ,MESH: Molecular Sequence Data ,MESH: X Chromosome ,MESH: Humans ,MESH: Transcription, Genetic ,Alternative splicing ,DNA Helicases ,Intron ,MESH: Polyglutamic Acid ,MESH: Polymerase Chain Reaction ,Sequence Analysis, DNA ,Introns ,Alternative Splicing ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Mutation ,MESH: Electrophoresis, Agar Gel ,MESH: Exons ,MESH: Nuclear Proteins - Abstract
International audience; The XNP/ATR-X gene is involved in several X-linked mental retardation phenotypes: the ATR-X syndrome, the Juberg-Marsidi syndrome, and some severe mental retardation phenotypes without alpha-thalassemia. Using a vectorette strategy, we have identified and sequenced the intron/exon boundaries of this gene. The gene is composed of 35 exons. It encodes a potential protein of 2492 amino acids. A search of the databases identified three zinc finger motifs within the 5' end of the gene. Expression analysis in different tissues indicated that an alternative splicing event that involves exon 6 is occurring. One of these alternatively spliced transcripts is predominantly expressed in embryonic tissues. These data led us to search for mutations in the 5' region in ATRX patients without other mutations in the 3' region. In one patient a mutation was found in which part of exon 7 was removed from the XNP transcript, as a result of a mutation creating a novel splice site that is substituted for the natural splice site. This new splicing event removed one zinc finger motif. This is the first example of a mutation in XNP within the 5' coding region. It suggests that mutations will be predominantly found in the helicase region as well as in the zinc finger regions and leads us to propose a large screening of additional patients.
- Published
- 1997
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