Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2

Neuromuscular Research Unit, University of Tampere, Tampere, Finland.
European journal of human genetics: EJHG (Impact Factor: 4.35). 04/2012; 20(11):1193-6. DOI: 10.1038/ejhg.2012.76
Source: PubMed


Spinal muscular atrophies (SMAs) are hereditary disorders characterized by degeneration of lower motor neurons. Different SMA types are clinically and genetically heterogeneous and many of them show significant phenotypic overlap. We recently described the clinical phenotype of a new disease in two Finnish families with a unique autosomal dominant late-onset lower motor neuronopathy. The studied families did not show linkage to any known locus of hereditary motor neuron disease and thus seemed to represent a new disease entity. For this study, we recruited two more family members and performed a more thorough genome-wide scan. We obtained significant linkage on chromosome 22q, maximum LOD score being 3.43 at marker D22S315. The linked area is defined by flanking markers D22S686 and D22S276, comprising 18.9 Mb. The region harbours 402 genes, none of which is previously known to be associated with SMAs. This study confirms that the disease in these two families is a genetically distinct entity and also provides evidence for a founder mutation segregating in both pedigrees.

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Available from: Sini Penttilä, Mar 09, 2015
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    ABSTRACT: We previously described two Finnish families with a new autosomal dominant late-onset spinal motor neuronopathy that was mapped to chromosome 22q11.2-q13.2. In the current screening study of 43 lower motor neuron disease patients from Finland and Sweden, we identified 26 new late-onset spinal motor neuronopathy patients sharing the founder haplotype. In addition to the main symptoms and signs: painful cramps, fasciculations, areflexia and slowly evolving muscle weakness, new features such as mild bulbar findings, were identified. The disease is relatively benign in terms of life expectancy and rate of disability progression, and it is therefore noteworthy that three patients were initially misdiagnosed with ALS. Significant recombinants in this new patient cohort restricted the disease locus by 90% to 1.8 Mb. Late-onset spinal motor neuronopathy seems not to be very rare, at least not in Finland, with 38 patients identified in a preliminary ascertainment.
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