Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I

Human Molecular Genetics
C BraheG Neri

Abstract

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 r...Continue Reading

Citations

Jul 13, 2002·Muscle & Nerve·Sophie NicoleJudith Melki
Apr 5, 2001·Journal of Biomedical Science·M Z HaiderL Reynold
May 20, 1998·Nature Genetics·C L LorsonE J Androphy
Jun 24, 1999·The New England Journal of Medicine·J B Martin
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J W FrancisR H Brown
Jul 30, 2014·Future Medicinal Chemistry·Matthew D HowellRavindra N Singh
Jun 22, 2002·Current Opinion in Genetics & Development·Tony FrugierJudith Melki
Jul 14, 2007·Neuromuscular Disorders : NMD·R LabrumA Krause
Jun 23, 1998·American Journal of Human Genetics·L CampbellK E Davies
Aug 6, 1999·Ryōikibetsu shōkōgun shirīzu·K SaitoM Osawa
Jan 1, 1997·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·K Talbot
May 3, 2001·Journal of Child Neurology·V Wong, V Chan
Jun 26, 2001·American Journal of Medical Genetics·S SrivastavaB Mittal
Mar 17, 2004·Human Mutation·Shuji Ogino, Robert B Wilson
Jul 21, 2001·European Journal of Human Genetics : EJHG·H SchefferB Wirth
Nov 7, 1998·Nature Genetics·D K GavrilovC H Wang
May 5, 1999·Current Opinion in Neurology·N H Gendron, A E MacKenzie
Apr 17, 2002·The Journal of Biological Chemistry·Hiroshi MiyajimaKazunori Imaizumi
Feb 27, 2003·The Journal of Biological Chemistry·Hidenobu MiyasoKazunori Imaizumi
Apr 17, 2001·Brain Pathology·H Schmalbruch, G Haase
Jul 17, 1999·Journal of Inherited Metabolic Disease·K Talbot
Mar 6, 2010·Journal of Proteome Research·Dina ShafeyRashmi Kothary

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.