Dissertations / Theses on the topic 'Hereditary motor neuropathy, HMN'
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Gopinath, Sumana. "Finding new genes causing motor neuron diseases." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1624.
Full textGopinath, Sumana. "Finding new genes causing motor neuron diseases." University of Sydney, 2006. http://hdl.handle.net/2123/1624.
Full textAbstract Neurodegenerative disorders are a diverse group of disorders that affect specific subsets of neurons. Motor neuron diseases, neurodegenerative disorders of motor neurons, are seen commonly as sporadic cases and less frequently as familial disease forms. The familial forms show genetic and phenotypic heterogeneity. Clinically motor neuron diseases may be seen as rapidly progressive disorders like amyotrophic lateral sclerosis, ALS or slowly progressive disorders like hereditary motor neuropathies, HMN. The only proven causes for motor neuron diseases are gene mutations that lead to motor neuron degeneration in familial disease forms. Only some of these genes have been identified and have contributed greatly to our understanding of the neurobiology of familial and sporadic disease forms. Identification of additional disease causing genes would help enhance our knowledge of the pathophysiological mechanisms underlying all forms of motor neuron disorders, which would lead to early diagnoses, effective prophylaxis and efficient therapies for these disorders. This study aimed to find gene mutations that cause rapid and slowly progressive familial motor neuron disorders in Australian families and to determine their relevance to sporadic forms of motor neuron disease. The familial forms of ALS show reduced disease penetrance, that is, not all gene mutation carriers manifest the disease. This study examines ALS penetrance in a group of Australian families. The most frequently observed mutations in ALS families are cytosolic superoxide dismutase/SOD1 gene mutations. In a collection of ALS families in our centre, families without the common SOD1 gene mutations were genotyped for other ALS genes and loci and studied using genetic linkage and haplotype analyses. Studies in a large Australian ALS family further confirmed genetic heterogeneity in non-SOD familial ALS, all known autosomal dominant ALS genes and chromosomal loci were excluded as cause of disease in this family. Such families can be studied further to identify additional disease genes and loci mapped in other ALS families. These families represent powerful resources for identification of additional ALS genes. Identifying the pathogenic genes in families with reduced disease penetrance may be more relevant to sporadic forms of disease. dHMN is a chronic neurodegenerative disorder predominantly affecting motor neurons. In a large Australian dHMN family, all the known dHMN genes and chromosomal loci were excluded as cause of disease. A genome wide microsatellite screen was performed in this family and genetic linkage was established to a novel 12.98 Mb locus on chromosome 7q34.2-q36. Candidate genes in this large interval will be screened based on their function and expression profile. Identification of a new dHMN locus provides the basis for future identification of a novel gene involved in motor neuron degeneration. Genes in dHMN have been shown to be pathogenic in ALS and Charcot Marie Tooth syndromes. The new locus for dHMN mapped in this project would lead to identification of a novel dHMN gene, which may elucidate the pathogenesis underlying a wide range of neurodegenerative disorders.
Drew, Alexander Peter. "Genetics of distal hereditary motor neuropathies." Thesis, The University of Sydney, 2012. http://hdl.handle.net/2123/8652.
Full textDati, Gabriele. "A transgenic mouse model of hereditary motor and sensory neuropathy." Thesis, Open University, 2009. http://oro.open.ac.uk/54643/.
Full textHantke, Janina. "Positional cloning of the gene mutated in hereditary motor and sensory neuropathy-russe (HMSNR)." Western Australian Institute for Medical Research, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0104.
Full textHantke, Janina. "Positional cloning of the gene mutated in hereditary motor and sensory neuropathy-russe (HMSNR) /." Connect to this title, 2004. http://theses.library.uwa.edu.au/adt-WU2005.0104.
Full textZabojova, Jorga. "Investigations into the molecular basis of spinal muscular atrophy and a novel form of hereditary motor neuropathy." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444949.
Full textHoward, Heidi C. "Identification of the gene responsible for peripheral neuropathy associated with agenesis of the corpus callosum." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84259.
Full textWe genotyped polymorphic markers in the ACCPN candidate region on chromosome 15 in over 67 patients and 200 control individuals. Observation of affected haplotypes confirmed the presence of a founder effect in the French Canadian population. Recombination analysis reduced the candidate interval to approximately 2 cM between markers D15S1040 and ACTC on chromosome 15. Linkage disequilibrium analysis suggested the gene resides nearest marker D15S1232. A physical map of the newly refined candidate region was constructed using YAC, BAC and PAC clones. These clones were used to confirm the position of candidate ESTs and genes as being either within or outside the ACCPN candidate region.
The connexin 36 gene, which was confirmed to reside within the region, was excluded as the gene responsible for ACCPN using SSCP analysis. The SLC12A6 gene was also confirmed to reside within the candidate interval and was tested for mutations using SSCP, dHPLC and sequence analyses. We found a total of four disease-specific mutations in SLC12A6, all of which are expected to truncate the KCC3 protein (the protein produced by the SLC12A6 gene). Two of the four mutations were identified in the French Canadian population; 80 French Canadian ACCPN patients are homozygous for the c.2436delG in exon 18 and one French Canadian patient is a compound heterozygote, having the c.2436delG mutation as well as the 1584_1585delCTinsG mutation in exon 11. Two additional mutations were identified in one Turkish and one Italian family in exons 22 and 15 respectively. The effects of the c.2436delG mutation on KCC3 function was studied in X. laevis oocytes and the truncated protein is not functional. Finally, collaborators at Vanderbilt University disrupted the slc12a6 gene in the mouse and found a phenotype similar to the human disease.
Identification of SLC12A6 as the gene mutated in ACCPN will allow for accurate molecular diagnosis as well as carrier testing in the French Canadian population. It is also the first step in understanding the molecular mechanism leading to the disease.
Barwick, Katy Elizabeth Sara. "Two newly defined inherited disorders due to cholinergic transporter dysfunction with distinct clinical outcomes, disease mechanisms and modes of inheritance." Thesis, University of Exeter, 2016. http://hdl.handle.net/10871/23407.
Full textAlves, Cyntia Rogean de Jesus. "Interação dos fatores musculoesqueléticos com o equilíbrio de crianças e adolescentes com neuropatia sensorial e motora hereditária." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17152/tde-19072018-161729/.
Full textPostural control in Charcot-Marie-Tooth disease (CMT) is supported in studies with adults, in which distal deformities, muscular imbalances and maturational aspects are well documented. For childhood and adolescence, standing balance remains to be explored and may contribute to elucidate how an immature neuromuscular system deals with the ongoing disease. In this context, a crosssectional study (Study 1) composed of children and adolescents with CMT (referred to the CMTInfantile Ambulatory of the HCFMRP-USP Rehabilitation Center, CMT Group) and their healthy peers (Control Group), and another longitudinal (Study 2), composed exclusively of children and adolescents with CMT were proposed. Study 1 characterized the postural oscillations and explored its interaction with musculoskeletal variables from the comparison of the CMT Group and Control Group, being composed of 53 participants of both sexes, age between 6 and 18 years, being 24 healthy and 29 with CMT. Mass, height, base of support, foot postural index (PPI), passive amplitudes of movement, isometric muscle strength of lower limbs, performance measures (6-min walk test -T6, 10- T10, horizontal jump - SH) and balance (stabilometry, Pediatric Balance Scale - EEP) were collected. The isometric muscle strength of the inversion, dorsiflexion, plantarflexion, knee extension, knee flexion and hip extension was measured bilaterally with a manual dynamometer (Lafayette, model 01163). Stabilometric evaluationused a force platform (Bertec, model FP 4060-08), with sampling frequency of 100 Hz, recording time of 30 s per trial. The 4 test conditions (open eyes / hard surface, open eyes / deformable surface, closed eyes / hard surface, closed eyes / deformable surface) were randomly repeated 3 times, intervals for 30 s, making 12 trials. The confidence ellipse area, velocity (total, mediolateral and anteroposterior), frequency (total, mediolateral and anteroposterior) and the Romberg Quotient (QRv) were extracted using MATLAB program (R2014a), adopting a 4th order Butterworth digital low-pass filter and a cut-off frequency of 7 Hz. Statistical analysis used the SPSS program (version 17) and it was adopted level of significance of 5%. In the musculoskeletal aspect (amplitude of dorsiflexion, popliteal angle and muscular strength of most of the groups tested) and performance tests (T10, T6 and SH), CMT group showed values lower than Control (p <0.05). For balance, intragroup comparisons of the test conditions in the CMT group evidenced an increased area and velocities of the pressure center (CP), but not the frequencies, according to the complexity of the task. In the intergroup comparisons, EEP and stabilometry showed less postural control in the CMT group when compared to the Control (increased confidence ellipse area and velocities associated with a decrease in CP frequency) (p <0.05). The most relevant interactions between musculoskeletal and oscillations of CP suggest better postural control for subjects the flat feet and reduced dorsiflexion amplitudes. Study 2 comprised 22 participants with CMT of both sexes, aged between 6 and 18 years and it sought to detect changes in postural oscillations in CMT with 6 and 12 consecutive months of follow-up. Postural oscillations, musculoskeletal and performance variables were analyzed at 6-month intervals (AV1, AV2 and AV3). SPSS (version 17) and R Core Team (2016) programs were used for statistical analysis. The Wilcoxon test was used to compare stabilometric variables of the bi-annual and annual follow-up and to a complementary analysis, considering the subgroups of 6 to 9 years (n = 8) and 10 to 17 years (n = 9). The linear mixed effects model analyzed the musculoskeletal variables. Student\'s t-test for paired samples was used to analyze T10, T6 and SH. The Fisher\'s exact test analyzed the IPP and EEP. The results showed no significant changes in the stabilometry between AV1 and AV2 or AV1 and AV3. Comparisons between AV1 and AV2 showed significant increase in the popliteal angle strength of the ankle evertors and hip extensors SH while the muscle strength of knee extensors decreased (p <0.05). Comparisons between AV1 and AV3, showed a significant increase in the muscular strength for inversion, eversion, dorsiflexion and knee extension groups (p <0.05). The complementary analysis of the annual follow-up identified significant reductions in dorsiflexion amplitude, mediolateral velocity (open eyes / rigid surface and closed eyes / rigid surface) and total velocity (open eyes / rigid surface and closed eyes / rigid surfaces) in the subgroup of children (n = 8) (p <0.05). Subgroup of adolescents (n = 9) showed a significant increase in the muscular strength of inverters, dorsiflexors and knee extensors (p <0.05) while the stabilometry remained unchanged. In summary, the results of Study 1 and 2 allow us to conclude that the poor postural control of children and adolescents with CMT is measurable based on the stabilometric variables extracted from the global analysis; is iv expressed by large and rapid CP oscillations, in which frequency does not distinguish the test conditions when compared to their healthy counterparts. The velocity of CP seems to reflect changes in postural stability when children and adolescents are analyzed as distinct subgroups. In addition, annual follow-up appears to be sufficient to detect changes in postural control, musculoskeletal and performance variables.
Costa, Iandra Maria Pinheiro de França. "Avaliação do equilíbrio, da força muscular e da funcionalidade de indivíduos com a doença de Charcot-Marie-Tooth." Universidade Federal de Sergipe, 2016. https://ri.ufs.br/handle/riufs/3615.
Full textA doença de Charcot-Marie-Tooth (CMT) é a neuropatia periférica geneticamente herdada mais frequente em todo mundo. A maioria dos casos de CMT pode ser classificada em duas grandes categorias quanto à natureza da lesão primária do nervo: CMT tipo 1 e tipo 2. As principais manifestações clínicas são fraqueza muscular e diminuição da sensibilidade nas pernas e pés, alterações na marcha e equilíbrio. Os objetivos deste estudo foram realizar uma revisão sistemática sobre o equilíbrio e funcionalidade de indivíduos com a doença de Charcot-Marie-Tooth (CMT), assim como avaliar a força muscular, o equilíbrio e funcionalidade de indivíduos com a doença de Charcot-Marie-Tooth tipo 2 (CMT2). Métodos: Uma pesquisa abrangente na literatura foi realizada utilizando como base de dados a MEDLINE-PubMed, Web of Science, Scopus (1980- 2015). Além disso, foi realizado um estudo observacional e transversal, por meio de entrevista e avaliação clínica de indivíduos com a doença de CMT2 no município de Tobias Barreto. A amostra foi composta por um grupo com 15 pacientes com CMT2(GCMT2) e um grupo controle (GC), com indivíduos saudáveis pareados por idades e gêneros com o grupo CMT2. Os indivíduos com CMT foram classificados pela escala neuropática de Charcot-Marie-Tooth (Charcot-Marie-Totth Neuropathy Score - CMTNS) que avalia o grau de severidade da doença. A força muscular foi avaliada através de um dinamômetro manual. O equilíbrio foi mensurado através do baropodômetro footwork e da escala de equilíbrio de Berg. A avaliação funcional foi mensurada pelo teste Timed Up Go (TUG). Resultados: Na revisão sistemática foram selecionados 18 artigos. Os tipos de estudo que prevaleceram foram sobre avaliação do equilibrio e funcionalidade, tratamento de reabilitação e evolução natural da doença de CMT. A maioria dos estudos encontrou que a fraqueza muscular e alterações da sensibilidade estavam relacionadas à perda de equilíbrio e menor desempenho das atividades funcionais. No segundo artigo, houve diferença estatisticamente significativa entre o GCMT2 e GC para força muscular de todos os músculos avaliados (dorsiflexores: p= < 0.0001, flexores plantares: p= < 0.0001, inversores: p= < 0.0001, eversores: p= 0.0016), para os parâmetros VCoPAP e DCopAP da estabilometria para olhos abertos e fechados respectivamente (p= 0,0123; p= 0,0183, p= 0,0132, p=0,0129), para a escala de equilíbrio de Berg (p=0,0066) e para o teste TUG ( p = 0.0003). As correlações mais evidentes foram entre todas as variáveis analisadas e o CMTNS. Além disso, indivíduos com CMT2 apresentam perda de equilíbrio no sentido ântero-posterior e com o aumento da severidade da doença esses indivíduos necessitam mais da visão para manutenção do equilíbrio. Conclusão: A maioria dos estudos da revisão sistemática que avaliaram equilibrio e/ou funcionalidade também incluiram em suas avaliações a mensuração da força muscular e sensibilidade. Além disso, os estudos mostraram que a fraqueza muscular distal, especialmente de dorsiflexores e flexores plantares, está associada à perda de equilíbrio em atividades dinâmicas e a posição estática, respectivamente. As avaliações clínicas, realizadas no grupo CMT2 e grupo controle, revelaram que pacientes com Charcot-Marie-Tooth têm menor equilíbrio e prejuízo das atividades funcionais quando comparados aos indivíduos saudáveis.
Amorim, Simone Consuelo de. "Estudo da condução nervosa em pacientes com a síndrome SPOAN." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-05112013-154543/.
Full textIntroduction: SPOAN syndrome (Spastic Paraplegia, Optic Atrophy and Neuropathy) is a progressive neurodegenerative disorder of autosomal recessive inheritance described by our group in a large inbred family from Northeastern Brazil. The clinical picture is characterized by non-progressive congenital optic atrophy, progressive spastic paraplegia, axonal neuropathy, auditory startles, dysarthria, spinal and foot deformities and also extrapyramidal signs. Linkage studies mapped the responsible locus for the syndrome to a 2Mb region on chromosome 11q13. The gene responsible for SPOAN syndrome remains elusive. Materials and Methods: This is a cross sectional study which was conducted from 2009 to 2011. We evaluated 27 patients (20 females), with a0ges ranging from 4 to 58 years. All patients shared the same phenotype (spastic paraplegia, optic atrophy and peripheral neuropathy) and had the same 11q13 haplotype in homozygosis. Patients with history of diabetes mellitus or alcoholism were excluded from this study. All patients were evaluated by the same clinical researcher (SA). Neurological evaluation included determination of modified neuropathy symptoms (NSS) and neuropathy disability (NDS) scores. Motor strength was assessed using MRC scale. Sensibility assessment included small-fiber (pain and temperature) and large-fiber modalities (vibration-128Hz diapason, 10g monofilament and joint position sense). Spine deformities and atrophy in the lower limbs were observed. We also evaluated osteotendineous reflexes and cutaneous plantar reflexes. Nerve conduction studies were performed using a portable Nicolet - Viking Quest, (Viasys,USA). Motor conduction studies included axillary, median, ulnar, femoral, tibial and fibular nerves on the right side. Sensory nerve action potentials of median, ulnar, sural and superficial fibular nerves were recorded using a bar electrode of 3 cm and standard fixed distances. Tibial H-reflex was evaluated with standard technique. Minimal F wave latencies were obtained from ulnar and tibial nerves. A few tests could not be done in every patient due to severe deformities. We calculated Pearson\'s correlation coefficients between age and nerve conduction parameters, including velocities, latencies and amplitudes. P values <0.05 were considered statistically significant. Results: Clinical data: Neuropathic symptoms such as pain and paresthesias were rare. All patients had signs of severe neuropathy. All subjects demonstrated weakness and atrophy that were more significant distally than proximally. Foot deformities were present in all patients and spine deformities were seen in 58%. Upper limb deep tendon reflexes were exalted in 92% and patelar reflex in 63%. Ankle reflex was absent in all patients. In one patient, who was 4 years-old, sensory evaluation was inconsistent and the results were not considered. In all the other ones, sensory modalities were affected and occurred predominantly in the lower limbs. Electrodiagnostic data: Sensory nerve conduction: Median nerve SNAP was absent in all 27 patients. Ulnar nerve SNAPs were absent in 96%, whereas radial nerve SNPAs were absent in 80%. Superficial fibular and sural SNAPs were absent in all patients. Motor nerve conduction: The motor latencies of axillary and femoral nerves were normal in all patients. CMAP amplitudes were reduced in 15% of the median nerves and in 52% of the ulnar nerves. Conduction velocities (CV) were reduced in 50% of the median nerves and in 41% of the ulnar nerves. CV was above 80% of the lower normal limit for all nerves, except for one patient who showed a 27% reduction of ulnar CV, but had also a CMAP amplitude of less than 2 mV. F waves were prolonged according to the height in 100%. Only one patient who presented significant motor CV reduction of the ulnar nerve. CMAPs were absent in 93% of the fibular nerves and in 84% of the tibial nerves. A single fibular nerve showed more than 20% of CV reduction, but also had severely reduced CMAP amplitude. H reflex was absent in 88% of the patients. There was no correlation between age and neurophysiological parameters, such as median or ulnar CV, latencies or CMAP amplitudes. Discussion: Nerve conduction studies in this group fulfill criteria for primary axonal neuropathy. No patient showed conduction block or temporal dispersion. Abnormalities seen in CV and F waves are probably related to loss of fast conduction fiber nerves. We could not demonstrate correlation between age and nerve conduction parameters, including velocities, latencies and amplitudes. SPOAN-like phenotype has been found in families with mutations in C12orf65, TFG and OPA1 genes, however there is no detailed report on nerve conduction studies in these conditions. Axonal neuropathy is also described in SPG55 and DOA plus, but usually with a later onset than on SPOAN syndrome. Peripheral neuropathy is also described in the family with mutation in TFG gene, but this presents a different pattern characterized as a mixed axonal demyelinating neuropathy with mild sensory involvement. Although the nerve conduction abnormalities seen in SPOAN syndrome are not specific, normal results seem to rule out this condition, at least in adult patients. The younger patient in our series was 4-years-old, and her neurophysiological study was severely abnormal, suggesting an early-onset neuropathy. However, we do not have a comprehensive study of several young patients to support that this feature is
Nývltová, Marcela. "Objektivizace poruch jemné motoriky horních končetin u pacientů s vrozenými neuropatiemi." Master's thesis, 2010. http://www.nusl.cz/ntk/nusl-281145.
Full textJílková, Daniela. "Vyšetření vegetativního systému u dědičné neuropatie." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-296724.
Full textOltrogge, Jan Hendrik. "Konditionale Inaktivierung von Pten in einem neuen Mausmodell für tomaculöse Neuropathien." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-002B-7D27-5.
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