caa a22 4500 397574827 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1737 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1737 A Repeated Element in the Regulatory Region of the MNK Gene and Its Deletion in A Patient With Occipital Horn Syndrome [Elektronische Daten] [Barbara Levinson, Rebecca Conant, Rhonda Schnur, Soma Das, Seymour Packman, Jane Gitschier] 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. © 1996 Oxford University Press Levinson Barbara Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut Conant Rebecca Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut Schnur Rhonda Children's Hospital of Philadelphia, Philadelphia, PA, USA aut Das Soma Department of Pediatrics, University of California, San Francisco, CA 94143, USA aut Packman Seymour Department of Pediatrics, University of California, San Francisco, CA 94143, USA aut Gitschier Jane Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1737-1742 0964-6906 5:11<1737 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1737 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1737 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Levinson Barbara Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut NATIONALLICENCE 700 1- Conant Rebecca Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut NATIONALLICENCE 700 1- Schnur Rhonda Children's Hospital of Philadelphia, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Das Soma Department of Pediatrics, University of California, San Francisco, CA 94143, USA aut NATIONALLICENCE 700 1- Packman Seymour Department of Pediatrics, University of California, San Francisco, CA 94143, USA aut NATIONALLICENCE 700 1- Gitschier Jane Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1737-1742 0964-6906 5:11<1737 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford