caa a22 4500 397573677 CHVBK 20180308164848.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/hmg/5.2.257 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.2.257 Molecular Analysis of the SMN and NAIP Genes in Spanish Spinal Muscular Atrophy (SMA) Families and Correlation between Number of Copies of cBCD541 and SMA Phenotype [Elektronische Daten] [Eladio Velasco, Carmen Valero, Ana Valero, Felipe Moreno, Concepción Hernández-Chico] Spinal muscular atrophy is an autosomal recessive disorder which affects about 1 in 10 000 individuals. The three clinical forms of SMA were mapped to the 5q13 region. Three candidate genes have been isolated and shown to be deleted in SMA patients: the Survival Motor Neuron gene (SMN), the Neuronal Apoptosis Inhibitory Protein gene (NAIP) and the XS2G3 cDNA. In this report we present the molecular analysis of the SMN exons 7 and 8 and NAIP exon 5 in 65 Spanish SMA families. NAIP was mostly deleted in type I patients (67.9%) and SMN was deleted in 92.3% of patients with severe and milder forms. Most patients who lacked the NAIP gene also lacked the SMN gene, but we identified one type II patient deleted for NAIP exon 5 but not for SMN exons 7 and 8. Two other patients carried deletions of NAIP exon 5 and SMN exon 7 but retained the SMN exon 8. Three polymorphic variants from the SMN gene, showing changes on the sequence of the centromeric (cBCD541) and telomeric copies of the SMN gene, were found. In addition, we show several genetic rearrangements of the telomeric SMN gene, which include duplication of this gene in one normal chromosome, and putative gene conversion events in affected and normal chromosomes. Altogether these results corroborate the high genetic variability of the SMA region. Finally, we have determined the ratio between the number of centromeric and telomeric copies of the SMN gene in parents of SMA patients, showing that the majority of parents of types II and III patients carried three or more copies of the cBCD541 gene; we suggest a relationship between the number of copies of cBCD541 and the disease phenotype. © 1996 Oxford University Press Velasco Eladio Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut Valero Carmen Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut Valero Ana Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut Moreno Felipe Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut Hernández-Chico Concepción Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut Human Molecular Genetics Oxford University Press 5/2(1996-02), 257-263 0964-6906 5:2<257 1996 5 hmg https://doi.org/10.1093/hmg/5.2.257 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.2.257 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Velasco Eladio Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut NATIONALLICENCE 700 1- Valero Carmen Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut NATIONALLICENCE 700 1- Valero Ana Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut NATIONALLICENCE 700 1- Moreno Felipe Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut NATIONALLICENCE 700 1- Hernández-Chico Concepción Unidad de Genética Molecular, Hospital Ramón y Cajal, Ctra. de Colmenar, km 9.1, 28034 Madrid, Spain aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/2(1996-02), 257-263 0964-6906 5:2<257 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