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

Katja Grohmann, Markus Schuelke, Alexander Diers, Katrin Hoffmann, Barbara Lucke, Coleen Adams, Enrico Bertini, Hajnalka Leonhardt-Horti, Francesco Muntoni, Robert Ouvrier, Arne Pfeufer, Rainer Rossi, Lionel Van Maldergem, Jo M. Wilmshurst, Thomas F. Wienker, Michael Sendtner, Sabine Rudnik-Schöneborn, Klaus Zerres, Christoph Hübner

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)75-77
Number of pages3
JournalNature Genetics
Volume29
Issue number1
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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