title: A repeated element in the regulatory region of the MNK gene and its deletion in a patient with occipital horn syndrome.
abstract: Occipital horn syndrome (OHS), an X-linked connective tissue disorder, has recently been shown to result from mutations in the Menkes disease gene (MNK), which encodes a copper-transporting ATPase. By Southern analysis we detected a small deletion in a region 5' to the MNK gene in one patient with OHS. Genomic clones from an unaffected individual were isolated and sequenced, revealing three tandem 98 bp repeats situated upstream of the reported transcription start site, and analysis of the patient's DNA showed a deletion of one of the repeats. The deletion is likely to be responsible for the disease in this patient, as it was not observed in 110 unaffected individuals analyzed, and no other mutation in the patient was detected by RT-PCR and chemical cleavage mismatch analysis or by cDNA sequence analysis. The deletion is associated with a dramatic decrease in expression of a chloramphenicol acetyltransferase reporter gene, implicating the repeat sequences in regulation of MNK expression, although a quantitative analysis of MNK mRNA from a cell line derived from the patient shows no detectable reduction. Other experiments revealed no effect on the site of transcription initiation, termination or on splicing.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
authors.forename: B
authors.initials: B
authors.lastname: Levinson
authors.forename: R
authors.initials: R
authors.lastname: Conant
authors.forename: R
authors.initials: R
authors.lastname: Schnur
authors.forename: S
authors.initials: S
authors.lastname: Das
authors.forename: S
authors.initials: S
authors.lastname: Packman
authors.forename: J
authors.initials: J
authors.lastname: Gitschier
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D000073840:Copper-Transporting ATPases; D003483:Cutis Laxa / Q000235:genetics*; D004252:DNA Mutational Analysis; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D017930:Genes, Reporter; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases