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Third-party-funded project

Title:
Identification of the underlying gene defect in Spinal Muscular Atrophy with respiratory distress (SMARD)

Project management at the University of Würzburg:

Participating scientists:

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 &mgr;-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 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.

Key words:
    Spinal muscular atrophy
    IGHMBP2
    IGHMBP2

Projekt period: from 01.2000 to 12.2001

Funding institution:
Sonstige Stiftung ( Schilling-Stiftung ) ,Granting date: 18.08.1998

Publications:

Links:
Institute for Clinical Neurobiology