Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on
chromosome 22q11.2-q13.2 |
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Authors: | Sini Penttil? Manu Jokela Peter Hackman Anna Maija Saukkonen Jari Toivanen Bjarne Udd |
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Institution: | 1.Neuromuscular Research Unit, University of
Tampere, Tampere, Finland;2.Department of Neurology, Turku University
Hospital, Turku, Finland;3.Department of Medical Genetics,
Folkhälsan Institute of Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland;4.Department of Neurology, Central Hospital of
Northern Karelia, Joensuu, Finland;5.Department of Neurology, Vasa Central
Hospital, Vasa, Finland |
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Abstract: | 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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Keywords: | motor neuron disease spinal muscular atrophy linkage analysis |
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