[ 14 , 17 , 38 , 51 ]. The studies with these models have shown that repeat RNA transcripts may contribute to dominantly inherited human pathology through multiple pathways [ 17 ]. Frontotemporaldementia (FTD) and ALS have similar genetic, clinical, and pathologic features [ 52 ]. The majority of patients with FTD develop features of motor neuron dysfunction [ 52 ], and nearly half of those with ALS are found to have evidence of frontal lobe impairment [ 52 ]. Amyotrophic lateral sclerosis is a fatal degenerative illness primarily affecting motor neurons, while FTD
References Neary D, Snowden JS, Mann DM. Classification and description of frontotemporaldementias. Ann NY Acad Sci 2000;920:46-51. Liscic RM, Storandt M, Cairns NJ, Morris JC. Clinical and psychometric distinction of frontotemporal and Alzheimer dementias. Arch Neurol 2007;64:535-40. Liscic R. How to differentiate frontotemporal from Alzheimer's dementia? Recent developments in molecular genetics and neuropathology. Zdrav Vestn 2008;77:71-4. Graham A, Davies R, Xuereb J, Halliday G, Kril J, Creasey H, Graham K, Hodges J. Pathologically proven
Molecular diagnosis relieves patients of uncertainty, aids informed decisions about health and reproductive choices, and helps them join clinical trials or access available therapy. Genetic testing by next generation sequencing (NGS) is the suggested choice for a wide variety of disorders with heterogeneous phenotypes, alleles and loci. The development of a NGS service at MAGI Balkans, through the support of a partner, increases the availability of forefront genetic testing in Albania with great advantages for patients and their families. Here we report the NGS tests performed in collaboration with MAGI Euregio, Italy, for the diagnosis of rare genetic disease in seven probands and their families. The diseases/manifestations included ichthyosis, familial adenomatous polyposis, diabetes, syndromic craniosynostosis, fronto-temporal dementia, fragile X syndrome and ataxia. We obtained an overall detection rate of 57%. For 4/7 probands we identified a pathogenic or likely pathogenic variant, while for the others, the results did not completely explain the phenotype. All variants were confirmed by Sanger sequencing. Segregation of the variant with the affected phenotype was also evaluated.
haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999; 8(4): 711-715. Morris HR, Khan MN, Janssen JC, Brown JM, Perez-Tur J, Baker M, Ozansoy M, Hardy J, Hutton M, Wood NW, Lees AJ, Revesz T, Lantos P, Rossor MN. The genetic and pathological classification of familial frontotemporaldementia. Arch Neurol 2001; 58(11): 1813-1816. Houlden H, Baker M, Adamson J, Grover A, Waring S, Dickson D, Lynch T, Boeve B, Petersen RC, Pickering-Brown S, Owen F, Neary D, Craufurd D, Snowden J, Mann D, Hutton M. Frequency of tau mutations in three series of
Neurological disorders are diseases of the brain, spine and the nerves that connect them. There are more than 600 diseases of the nervous system, such as epilepsy, Parkinson's disease, brain tumors, and stroke as well as less familiar ones such as multiple sclerosis or frontotemporal dementia. The increasing capabilities of neurotechnologies are generating massive volumes of complex data at a rapid pace. Evaluating and diagnosing disorders of the nervous system is a complicated and complex task. Many of the same or similar symptoms happen in different combinations among the different disorders. This paper provides a survey of developed selected data mining methods in the area of neurological diseases diagnosis. This review will help experts to gain an understanding of how data mining techniques can assist them in neurological diseases diagnosis and patients treatment.
The tubulin cytoskeleton is vital for maintenance and dynamics of eukaryotic cells and molecular defects in its components can lead to serious conditions. So far, mutations in genes for alpha-, beta- and gamma-tubulin, motor proteins of the kinesin and dynein family, microtubule-associated and centrosomal proteins have been found to cause disorders in humans. Most phenotypic effects are on the nervous system, leading to abnormal brain development (e.g. lissencephaly and microcephaly) or to neurodegeneration in later life (e.g. amyotrophic lateral sclerosis and frontotemporal dementia). Another group of disorders include the ciliopathies, caused by defects in the axoneme. They include primary ciliary dyskinesia (immotile cilia syndrome), which is characterized by chronic respiratory infections, male infertility and randomly established left-right asymmetry. In most cases, the underlying defects are in axonemal dynein. Mutations in genes for centrosomal components have been shown to cause cortical dysplasia and dwarfism by disrupting the mitotic spindle, and some cases of infertility with maturation arrest are likely to be caused by unidentified mutations damaging the meiotic spindle. In view of these diverse phenotypes, knowledge about mutations affecting tubulin cytoskeleton becomes increasingly useful for clinical practice.
et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010; 68:857-864. 9. DeJesus-Hernandez M, Mackenzie I, Bradley F. Boeve et al. Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked frontotemporaldementia and amyotrophic lateral sclerosis. Neuron. 2011 October 20; 72(2): 245-256. doi: 10.1016/j.neuron.2011.09.011. 10. Renton AE, Majounie E, Waite A et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011 Oct 20;72(2):257-68. doi: 10
, et al. Extrastriatal dopaminergic changes in Parkinson’s disease patients with impulse control disorders. J Neurol Neurosurg Psychiatry 2014;85:23-30. 11. O’Callaghan C, Naismith SL, Hodges JR, Lewis SJ, Hornberger M. Fronto-striatal atrophy correlates of inhibitory dysfunction in Parkinson’s disease versus behavioural variant frontotemporaldementia. Cortex 2013;49:1833-43. 12. O’Callaghan C, Moustafa AA, de Wit S, Shine JM, Robbins TW, Lewis SJ, et al. Fronto-striatal gray matter contributions to discrimination learning in Parkinson’s disease. Front Comput
. Journal of Molecular Medicine. 2003; 81(10): 600-612. 25. BAKER M, MACKENZIE IR, PICKERING-BROWN SM, GASS J, RADEMAKERS R, LINDHOLM C, et al. Mutations in progranulin cause-negative frontotemporaldementia linked to chromosome 17. Nature. 2006; 442: 916-919. 26. CRUTS M, GIJSELINCK I, VAN DER ZEE J, ENGELBORGHS S, WILS H, PIRICI D, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporaldementia linked to chromosome 17q21. Nature. 2006; 442: 920-924. 27. DANIEL R, DANIEL E, HE Z, BATEMAN A. Progranulin (acrogranin/PC cell-derived growth factor