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.
| Original language | English |
|---|---|
| Pages (from-to) | 75-77 |
| Number of pages | 3 |
| Journal | Nature Genetics |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2001 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Mutations in the gene encoding immunoglobulin μ-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. / Grohmann, Katja; Schuelke, Markus; Diers, Alexander; Hoffmann, Katrin; Lucke, Barbara; Adams, Coleen; Bertini, Enrico; Leonhardt-Horti, Hajnalka; Muntoni, Francesco; Ouvrier, Robert; Pfeufer, Arne; Rossi, Rainer; Van Maldergem, Lionel; Wilmshurst, Jo M.; Wienker, Thomas F.; Sendtner, Michael; Rudnik-Schöneborn, Sabine; Zerres, Klaus; Hübner, Christoph.
In: Nature Genetics, Vol. 29, No. 1, 2001, p. 75-77.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutations in the gene encoding immunoglobulin μ-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1
AU - Grohmann, Katja
AU - Schuelke, Markus
AU - Diers, Alexander
AU - Hoffmann, Katrin
AU - Lucke, Barbara
AU - Adams, Coleen
AU - Bertini, Enrico
AU - Leonhardt-Horti, Hajnalka
AU - Muntoni, Francesco
AU - Ouvrier, Robert
AU - Pfeufer, Arne
AU - Rossi, Rainer
AU - Van Maldergem, Lionel
AU - Wilmshurst, Jo M.
AU - Wienker, Thomas F.
AU - Sendtner, Michael
AU - Rudnik-Schöneborn, Sabine
AU - Zerres, Klaus
AU - Hübner, Christoph
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=17944374029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17944374029&partnerID=8YFLogxK
U2 - 10.1038/ng703
DO - 10.1038/ng703
M3 - Article
C2 - 11528396
AN - SCOPUS:17944374029
VL - 29
SP - 75
EP - 77
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -