SNP array-based whole genome homozygosity mapping as the first step to a molecular diagnosis in patients with Charcot-Marie-Tooth disease
| Autor: | Michaela Auer-Grumbach, G. Bernert, Wolfgang Löscher, Slave Trajanoski, Maria Schabhüttl, Lea Papić, Jan Senderek, Barbara Plecko, Mine Arslan-Kirchner, Andreas R. Janecke, Michael Freilinger, Poupak Javaher-Haghighi, C. Rauscher, Carina Fischer, Christian Windpassinger, Thomas R. Pieber |
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| Přispěvatelé: | University of Zurich, Auer-Grumbach, Michaela |
| Rok vydání: | 2011 |
| Předmět: |
Male
DNA Mutational Analysis HSP27 Heat-Shock Proteins Genome Gene GTP Phosphohydrolases 0302 clinical medicine Charcot-Marie-Tooth Disease SH3TC2 Genotype Child Heat-Shock Proteins Oligonucleotide Array Sequence Analysis Genetics 0303 health sciences Original Communication Intracellular Signaling Peptides and Proteins Chromosome Mapping Middle Aged Disease gene identification 3. Good health 2728 Neurology (clinical) Neurology Female SNP array Adult Adolescent Clinical Neurology Hereditary neuropathies 610 Medicine & health Biology Polymorphism Single Nucleotide DNA sequencing Mitochondrial Proteins 03 medical and health sciences Young Adult Homozygosity mapping SNP Humans Genetic Predisposition to Disease 030304 developmental biology Gene Expression Profiling Proteins Gene expression profiling 10036 Medical Clinic 2808 Neurology Neurology (clinical) Autosomal recessive CMT 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | Journal of Neurology |
| ISSN: | 1432-1459 |
| Popis: | Considerable non-allelic heterogeneity for autosomal recessively inherited Charcot-Marie-Tooth (ARCMT) disease has challenged molecular testing and often requires a large amount of work in terms of DNA sequencing and data interpretation or remains unpractical. This study tested the value of SNP array-based whole-genome homozygosity mapping as a first step in the molecular genetic diagnosis of sporadic or ARCMT in patients from inbred families or outbred populations with the ancestors originating from the same geographic area. Using 10 K 2.0 and 250 K Nsp Affymetrix SNP arrays, 15 (63%) of 24 CMT patients received an accurate genetic diagnosis. We used our Java-based script eHoPASA CMT—easy Homozygosity Profiling of SNP arrays for CMT patients to display the location of homozygous regions and their extent of marker count and base-pairs throughout the whole genome. CMT4C was the most common genetic subtype with mutations detected in SH3TC2, one (p.E632Kfs13X) appearing to be a novel founder mutation. A sporadic patient with severe CMT was homozygous for the c.250G > C (p.G84R) HSPB1 mutation which has previously been reported to cause autosomal dominant dHMN. Two distantly related CMT1 patients with early disease onset were found to carry a novel homozygous mutation in MFN2 (p.N131S). We conclude that SNP array-based homozygosity mapping is a fast, powerful, and economic tool to guide molecular genetic testing in ARCMT and in selected sporadic CMT patients. Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6213-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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