Abstract |
Spinal Muscular Atrophy with Respiratory Distress (SMARD) is an autosomal recessive disorder characterized by neurogenic muscular atrophy due to progressive anterior horn cell degeneration and early life-threatening respiratory failure ascribed to diaphragmatic dysfunction. SMARD is clinically and genetically heterogeneous. SMARD type 1 is characterized by onset of respiratory failure within the first weeks of life and has been ascribed to mutations in the immunoglobulin mu- binding protein 2 (IGHMBP2) gene on chromosome 11q13-q21. We report here the identification of nine novel IGHMBP2 mutations in five SMARD1 patients, including seven missense [ c.587A>G (p.Gln196Arg), c.647C>T (p.Pro216Leu), c.752T>C (p.Leu251Pro), c.1693G>A (p.Asp565Asn), c.1730T>C (p.Leu577Pro), c.1807C>T (p.Arg603Cys), c.1909C>T (p.Arg637Cys)] and two nonsense mutations [ c.1488C>A (p.Cys496X), c.2368C>T (p.Arg790X)]. Interestingly, 7 of 9 mutations occurred at highly conserved residues of the putative DNA helicase domain. The identification of novel IGHMBP2 variants will hopefully help diagnosing SMARD1 and contribute to a better functional characterization of IGHMBP2 gene product.
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Authors | I Maystadt, M Zarhrate, P Landrieu, O Boespflug-Tanguy, S Sukno, P Collignon, J Melki, C Verellen-Dumoulin, A Munnich, L Viollet |
Journal | Human mutation
(Hum Mutat)
Vol. 23
Issue 5
Pg. 525-6
(May 2004)
ISSN: 1098-1004 [Electronic] United States |
PMID | 15108294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2004 Wiley-Liss, Inc. |
Topics |
- Alleles
- Humans
- Infant
- Infant, Newborn
- Mutation
- Spinal Muscular Atrophies of Childhood
(diagnosis, genetics)
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