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Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1

Item Type:Article
Title:Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1
Creators Name:Grohmann, K. and Schuelke, M. and Diers, A. and Hoffmann, K. and Lucke, B. and Adams, C. and Bertini, E. and Leonhardt-Horti, H. and Muntoni, F. and Ouvrier, R. and Pfeufer, A. and Rossi, R. and Van Maldergem, L. and Wilmshurst, J.M. and Wienker, T.R. and Sendtner, M. and Rudnik-Schoeneborn, S. and Zerres, K. and Huebner, C.
Abstract:Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1. Its product is involved in various cellular processes, including cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA processing and activation of transcription. Spinal muscular atrophy with respiratory distress (SMARD) is clinically and genetically distinct from SMA. Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin μ-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4). In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus. Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals.
Keywords:Amino Acid Sequence, Amino Acid Sequence Homology, Base Sequence, Carrier Proteins, DNA Primers, DNA-Binding Proteins, Molecular Sequence Data, Missense Mutation, Newborn Respiratory Distress Syndrome, Pair 11 Human Chromosomes, Pedigree, Spinal Muscular Atrophy, Transcription Factors, Animals, Mice
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group (U.S.A.)
Volume:29
Number:1
Page Range:75-77
Date:1 January 2001
Official Publication:https://doi.org/10.1038/ng703
PubMed:View item in PubMed

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