caa a22 4500 397573545 CHVBK 20180308164848.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1971 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1971 Frameshift Mutation in the Survival Motor Neuron Gene in a Severe Case Of SMA Type I [Elektronische Daten] [Christina Brahe, Olivier Clermont, Stefania Zappata, Francesco Tiziano, Judith Melki, Giovanni Neri] Recently, a spinal muscular atrophy (SMA) determining gene, termed survival motor neuron (SMN) gene, has been isolated from the 5q13 region and found deleted in most patients. A highly homologous copy of this gene has also been isolated and located in a centromeric position. We have analyzed 158 patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%. Mutations other than gross deletions seem to be extremely rare. In one of the undeleted SMA type I patients, a newborn who survived for only 42 days, we detected a maternally inherited 5 bp microdeletion in exon 3, resulting in a premature stop codon. By RT- PCR and long range PCR amplification we were able to show that the deletion belongs to the SMN gene, rather than to the centromeric copy, and that the proposita had no paternal SMN gene. Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which maps close to SMN and has been proposed as a SMA modifying gene, suggests the presence of at least one full-length copy. Haplotype analysis of closely linked polymorphic markers suggests that the proposita also lacks the maternally derived copy of the centromeric homologue of SMN supporting the hypothesis that the severity of the phenotype might depend on the reduced number of centromeric genes in addition to the frameshift mutation. © 1993 Oxford University Press Brahe Christina Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut Clermont Olivier Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants Malades, 75743 Paris, France aut Zappata Stefania Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut Tiziano Francesco Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut Melki Judith Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants Malades, 75743 Paris, France aut Neri Giovanni Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1971-1976 0964-6906 5:12<1971 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1971 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1971 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Brahe Christina Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut NATIONALLICENCE 700 1- Clermont Olivier Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants Malades, 75743 Paris, France aut NATIONALLICENCE 700 1- Zappata Stefania Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut NATIONALLICENCE 700 1- Tiziano Francesco Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut NATIONALLICENCE 700 1- Melki Judith Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital des Enfants Malades, 75743 Paris, France aut NATIONALLICENCE 700 1- Neri Giovanni Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Facoltà di Medicina e Chirurgia ‘A. Gemelli', I-00168 Rome, Italy aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1971-1976 0964-6906 5:12<1971 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