caa a22 4500 397573219 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1727 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1727 An 11 Base Pair Duplication in Exon 6 of the SMN Gene Produces a Type I Spinal Muscular Atrophy (SMA) Phenotype: Further Evidence For SMN as the Primary SMA-Determining Gene [Elektronische Daten] [D. Williams Parsons, Patricia E. McAndrew, Umrao R. Monani, Jerry R. Mendell, Arthur H. M. Burghes, Thomas W. Prior] The gene for autosomal recessive spinal muscular atrophy (SMA) has been mapped to 5q12 in a region that contains repeated markers and genes. Three cDNAs that detect deletions in SMA patients have been reported. One of these, the survival motor neuron (SMN) cDNA, is encoded by two genes (SMNT and SMNC) which are distinguished by base changes in exons 7 and 8. Exon 7 of the SMNT gene is not detectable in ∼95% of SMA cases, due either to deletion or sequence conversion. There is limited information on the mutations in SMA patients that have detectable SMNT: these are critical for confirmation of SMNT as the SMA gene. Using SSCP analysis of the SMN exons we screened our SMA patients that possess at least one intact SMNT allele for mutations in SMNTT. We identified one type I SMA patient with an 11 bp duplication in exon 6 which causes a frameshift and premature termination of the deduced SMNT protein. Dosage and SSCP analysis of SMNT in this family indicated that the father contributed a SMNT-deleted allele to the affected child whereas the mother passed on the 11 bp exon 6 duplication SMNT allele. Analysis of RNA by RT-PCR conclusively demonstrated that the 11 bp duplication is associated with the SMNT locus and not SMNC. This mutation provides strong support for SMN as the SMA-determining gene and indicates that disruption of SMNT on its own is sufficient to produce a severe type I SMA phenotype. © 1996 Oxford University Press Parsons D. Williams Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut McAndrew Patricia E. Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut Monani Umrao R. Department of Molecular Genetics, College of Biological Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut Mendell Jerry R. Department of Neurology, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut Burghes Arthur H. M. Department of Molecular Genetics, College of Biological Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut Prior Thomas W. Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1727-1732 0964-6906 5:11<1727 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1727 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1727 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Parsons D. Williams Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 700 1- McAndrew Patricia E. Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 700 1- Monani Umrao R. Department of Molecular Genetics, College of Biological Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 700 1- Mendell Jerry R. Department of Neurology, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 700 1- Burghes Arthur H. M. Department of Molecular Genetics, College of Biological Sciences, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 700 1- Prior Thomas W. Department of Pathology, Molecular Pathology Laboratory, The Ohio State University College of Medicine, Columbus, OH 43210, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1727-1732 0964-6906 5:11<1727 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