Preferencje help
Polish version English version Język
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 17

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
1

De novo Ser72Leu mutation in the peripheral myelin protein 22 in two Polish patients with a severe from of Charcot-Marie-Tooth disease

100%
Kochanski A., Kabzinska D.
Acta Biochimica Polonica
|
2004
|
tom 51
|
nr 4
To date, 12 cases of heterozygous Ser72Leu mutations in the peripheral myelin protein 22 have been reported in patients suffering from severe demyelinating form of Charcot-Marie-Tooth disease (CMT1) and congenital hypomyelinating neuropathy (CHN) [MIM# 605253]. In the present study we report two cases of de novo S72L mu­tations in the PMP22 gene detected in patients of Polish origin suffering from CMT1 disease.
2

Molecular genetic analysis of the GJB1 gene: a study of six mutations

100%
Kochanski A., Kabzinska D.
Journal of Applied Genetics
|
2004
|
tom 45
|
nr 1
3

Screening of the 17p11.2-p12 region in a large cohort of patients with Charcot-Marie-Tooth [CMT] disease or hereditary neuropathy with liability to pressure palsies [HNPP]

81%
Kabzinska D., Pierscinska J., Kochanski A.
Journal of Applied Genetics
|
2009
|
tom 50
|
nr 3
283-288
Within the last decade, numerous methods have been applied to detect the most common mutation in patients affected with Charcot-Marie-Tooth (CMT) disease, i.e. submicroscopic duplication in the 17p11.2-p12 region. In 1993, another neuropathy - known as hereditary neuropathy with liability to pressure palsies (HNPP) - has been shown to be caused by a 17p11.2-p12 deletion. Historically, Southern blot analysis was the first approach to identify CMT1A duplication or HNPP deletion. This time- and labor-consuming method requires prior selection of DNA samples. In fact, only CMT patients affected with the demyelinating form of CMT1 have been screened for CMT1A duplication. After the 17p11.2-p12 duplication was identified in the CMT1 families, subsequent studies revealed additional axonal features in the patients harboring the 17p11.2-p12 duplication. Thus it seems reasonable to test all patients affected with CMT for the presence of the 17p11.2-p12 duplication. To evaluate the utility of real-time polymerase chain reaction (Q-PCR) and restriction fragment length polymorphism PCR (RFLP-PCR), we screened a large group of 179 families with the diagnosis of CMT/HNPP for the presence of the 17p11.2-p12 duplication/deletion. Due to a high frequency of CMT1A duplication in familial cases of CMT, we propose (in contrast to the previous studies) to perform Q-PCR analysis in all patients diagnosed with CMT.
4

Can different expression of mitofusins be involved in pathomechanism of particular mitochondrial diseases?

81%
Kawalec M., Neska J., Kabzinska D., Zablocka B.
Acta Neurobiologiae Experimentalis
|
2013
|
tom 73
|
nr 1
Mitochondrial homeostasis, resulting from fusion and fission processes together with mitophagy and mitogenesis, are widely studied nowadays. This is probably because we know more and more about the role of mitochondria in metabolic diseases (diabetes, hypertension), neurodegeneration (Parkinson’s Disease, Alzheimer’s Disease), but also in broad spectrum of inherited neurological syndromes (CharcotMarie-Tooth). In our studies we aimed to examine the expression pattern of particular mitochondrial proteins, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), in mouse tissues. We aim to verify, whether potential differences in expression of those proteins can by implicated in pathomechanism of Charcot-Marie-Tooth type 2A neuromyopathy, related to mitofusion 2 gene mutations. Mitofusins are mitochondrial GTPases, implicated in fusion of outer mitochondrial membrane. In this process, mitofusins juxtapose two mitochondria by combining homo- and heterodimers at the surface of two outer mitochondrial membranes. Although there is 63% homology between mitofusins, it is proved, that they show some different functions. As Mfn1 KO present more severe aberrations in mitochondrial network formation than Mfn2 deficient cells, Mfn1 is considered to have stronger fusion activity. It is also suspected, that it is Mfn1 that links fusion of outer and inner mitochondrial membranes. Nevertheless, Mfn2, but not Mfn1, is present at endoplasmic reticulum (ER). Mfn2 tethers ER to mitochondria facilitating calcium flux and (indirectly) autophagy. Moreover, Mfn2 seems to have some regulatory effect on cell cycle, beyond its fusion activity and its lower expression seems to correlate with insulin resistance and hyper proliferation in hypertension. So, the question is, how much these two proteins can replace each other while playing so different roles? Moreover, it is suggested that CMT2A predominantly affects peripheral nerves because mutated, malfunctioned Mfn2 is insufficiently compensated by Mfn1 due to its low expression particularly in this type of tissue. To discuss this issue, we have investigated the expression of Mfn1 and Mfn2, as well as protein content, in tissues, performing Real Time PCR and Western Blot studies. Preliminary data from Western blot analysis displayed equally high relative level of both mitofusins in nervous system (dorsal root ganglia, cerebral cortex, cerebellum, spinal cord) in comparison to peripheral organs (muscle, heart, liver, kidney, skin). Moreover, Mfn1 expression seems significantly lower in dorsal root ganglia, which are well established model of peripheral nervous system. This phenomenon was not observed for other tissues, even from central nervous system. So it seems quite possible, that axonal damage of peripheral nerves in CMT2A, may be observed due to the poor compensation of dysfunctional Mfn2 by fully functional Mfn1, which is not expressed at sufficient level. The project was supported by NSC grant NN402474640
5

Molecular pathogenesis, experimental therapy and genetic counseling in hereditary sensory neuropathies

81%
Mroczek M., Kabzinska D., Kochanski A.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr 2
Hereditary sensory and autonomic neuropathies (HSANs) represent a group of heritable peripheral nerve disorders usually taking a severe clinical course. HSAN-affected patients manifest with deep, poorly-healing ulcerations of the feet and hands. To date no definitive cure for HSANs has been developed and the molecular pathology of these disorders is complex. The aim of this review is therefore to present recent findings-in terms of HSAN molecular pathogenesis. So far, mutations in 12 genes coding for different proteins have been reported in association with HSAN and the molecular pathogenesis has been elucidated in HSANla, HSAN4 and HSAN5. The genes involved in molecular pathogenesis of HSAN code for a wide spectrum of proteins from enzymes to specific nerve growth factors. As far as HSANla is concerned, the enhanced understanding has given rise to achievements in experimental therapy particularly in respect to disease models. Despite a rapid progress in studies on the molecular background of HSAN, numerous loci and genes remain still to be discovered.
6

Two pathogenic mutations located within the 5'-regulatory sequence of the GJB1 gene affecting initiation of transcription and translation

81%
Kabzinska D., Kotruchow K., Ryniewicz B., Kochanski A.
Acta Biochimica Polonica
|
2011
|
tom 58
|
nr 3
 In contrast to mutations in the coding sequences of a genes involved in the pathogenesis of Charcot-Marie-Tooth disease (CMT), little is known about CMT phenotypes resulting from a DNA variants located in regulatory sequences of a given " CMT gene". Charcot-Marie-Tooth type X1 disease (CMTX1) is caused by mutations in the GJB1 gene coding for an ion channel known as connexin, with a molecular mass of 32 kDa (Cx32). Only 0.01% of the GJB1 gene mutations have been reported in its 5' regulatory sequence. Pathogenic mutations occured in the internal ribosome entry site (IRES) are extremely rarely reported in human genetic disorders. To the best of our knowledge, in this study we report for the first time in an Eastern European population, two CMTX1 families in which two pathogenic mutations in the 5' regulatory sequence of the GJB1 gene (c.-529T>C and -459C>T) have been found. The two mutations identified in our study disturb the 5' UTR sequence in two different ways, by affecting the transcription factor SOX10 binding site (c.-529T>C) and by the disrupting IRES element of GJB1 gene (c.-459C>T). These regions are responsible for transcription (SOX10) and initiation of translation (IRES), respectively. On the basis of our findings that, in contrast to the most DNA sequence variants reported in untranslated regulatory regions of genes, the c.-459C>T and c.-529T>C mutations remain pathogenic in the context of different ethnic background.
7

A newly identified Thr99fsX110 mutation in the PMP22 gene associated with an atypical phenotype of the hereditary neuropathy with liability to pressure palsies

81%
Moszynska I., Kabzinska D., Sinkiewicz-Darol E., Kochanski A.
Acta Biochimica Polonica
|
2009
|
tom 56
|
nr 4
627-630
 Hereditary neuropathy with liability to pressure palsies (HNPP) is manifested by a spectrum of phenotypes, from the classical HNPP course associated with intermittent nerve palsies to a neuropathy resembling Charcot-Marie-Tooth type 1 (CMT1) disease. The majority of HNPP cases are associated with submicroscopical deletions in the 17p11.2-p12 region containing the PMP22 gene, while PMP22 point mutations are rare, representing about 15% of HNPP cases. In this study, we present a patient manifesting with atypical HNPP phenotype associated with a new Thr99fsX110 mutation in the PMP22 gene. We conclude that all patients who fulfill the electrophysiological criteria of HNPP, even if they lack the typical HNPP phenotype, should be tested for point mutations in the PMP22 gene.
8

Charcot-Marie-Tooth type 1A disease caused by a novel Ser112Arg mutation in the PMP22 gene, coexisting with a slowly progressive hearing impairment

81%
Kabzinska D., Sinkiewicz-Darol E., Hausmanowa-Petrusewicz I., Kochanski A.
Journal of Applied Genetics
|
2010
|
tom 51
|
nr 2
203-209
Among 57 mutations in the peripheral myelin protein 22 gene (PMP22) identified so far in patients affected by Charcot-Marie-Tooth disease (CMT), only 8 have been shown to segregate with a mixed phenotype of CMT and hearing impairment. In this study, we report a new Ser112Arg mutation in the PMP22 gene, identified in a patient with early-onset CMT and slowly progressive hearing impairment beginning in the second decade of life. We suggest that the Ser112Arg mutation in the PMP22 gene might have a causative role in the early-onset CMT with hearing impairment. Thus, our study extends the spectrum of CMT phenotypes putatively associated with PMP22 gene mutations.
9

The 5' regulatory sequence of the PMP22 in the patients with Charcot-Marie-Tooth disease

81%
Sinkiewicz-Darol E., Kabzinska D., Moszynska I., Kochanski A.
Acta Biochimica Polonica
|
2010
|
tom 57
|
nr 3
Little is known about the molecular background of clinical variability of Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A and HNPP disorders result from duplication and deletion of the PMP22 gene respectively. In a series of studies performed on affected animal transgenic models of CMT1A disease, expression of the PMP22 gene (gene dosage) was shown to correlete with severity of CMT course (gene dosage effect). In this study we hypothesized that single nucleotide polymorphisms (SNPs) located within the 5' regulatory sequence of PMP22 gene may be responsible for the CMT1A/HNPP clinical variability. We have sequenced the PMP22 5' upstream regulatory sequence in a group of 45 CMT1A/HNPP patients harboring the PMP22 duplication (37) /deletion (8). We have identified five SNPs in the regulatory sequence of the PMP22 gene. Three of them i.e. -819C>T, -4785G>T, -4800C>T were detected both in the patients and in the control group. Thus, their pathogenic role in the regulation of the expression of the PMP22 gene seems not to be significant. Two SNPs i.e. -4210T>C and -4759T>A were found only in the CMT patients. Their role in the regulation of the PMP22 gene expression can not be excluded. Additionally we have detected the Thr118Met variant in exon 4 of the PMP22 gene, which was previously reported by other authors, in one patient. We conclude that the 5' regulatory sequence of the PMP22 gene is conserved at the nucleotiode level, however rarely occurring SNPs variant in the PMP22 regulatory sequence may be associated with the gene dosage effect.
10

Patogeneza molekularna choroby Charcot-Marie-Tooth 2

81%
Kotruchow K., Kabzinska D., Karpinska K., Kochanski A.
Postępy Biochemii
|
2011
|
tom 57
|
nr 3
11

Pathogenic mutations and sequence variants within mitofusin 2 gene in Polish patients with different hereditary motor-sensory neuropathies

81%
Kotruchow K., Kabzinska D., Kochanski A.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr 3
At the time of its first description in 2004, MFN2 was considered the most frequently mutated gene in hereditary motor and sensory neuropathy type 2 (HMSN 2). However recent studies have shown that the frequency of MFN2 gene mutations in HMSN II patients is surprisingly low. To date, no systematic studies devoted to HMSN Ila in Poland have been carried out. In this study, we searched for MFN2 gene mutations in Polish patients representing the population of nearly 40 million. We decided to include a wide spectrum of clinical phenotypes in the study, proving able to detect, in a group of 67 affected patients: 1) 3 pathogenic mutations 2) 3 sequence variants of unknown pathogenic status 3) 9 rare MFN2 gene sequence variants 4) 6 common polymorphisms The frequency of MFN2 gene mutations in the whole group of patients is 4.5%. Due to the high frequency of MFN2 gene sequence variants within single patients we could not definitely exclude the cumulative effect of these contributing to the HMSN II phenotype. The MFN2 gene should therefore be considered in Polish HMSN II patients, though it is still not possible to determine its position in HMSN II molecular diagnostics.
12

LITAF and TNF alpha genes sequence variants in the patients with Charcot-Marie-Tooth disease

71%
Sinkiewicz-Darol E., Potulska-Chromik A., Kostera-Pruszczyk A., Kabzinska D., Kochanski A.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr 1
Recently it has been reported that Charcot-Marie-Tooth disease may coexist with chronic inflammatory neuropathy and central demyelination. There is a question, whether CMT and inflammatory disease detected in one family share a common pathogenesis or result from the random coincidence of two disorders. There is a possibility that mutations/sequence variants in the gene coding for immune response mediators (LITAF, TNF alpha) may modify the CMT phenotype. To test this hypothesis, we have sequenced the coding sequence of LITAF gene and the promoter sequence of TNF alpha gene in two families with Charcot-Marie-Tooth disease coexisting with chronic inflammatory demyelinating polyneuropathy (CIDP) and primary progressive multiple sclerosis (PPMS). The genetic analysis has revealed three sequence variants: c.274A>G (Ile92Val) and in c.334G>A (Gly112Ser) in the LITAF gene and one SNP -308G>A in the promoter region of TNF alpha gene. The sequence variants c.334G>A (Gly112Ser) in the LITAF gene and -308G>A in the TNF alpha gene were detected in family with Charcot-Marie-Tooth type 1C and primary progressive multiple sclerosis (PPMS). The sequence variants c.274A>G (Ile92Val) in the LITAF gene and -308G>A in the TNF alpha gene were detected in family with Charcot-Marie-Tooth type 1A and chronic inflammatory polyradiculoneuropathy (CIDP). In agreement with previously published data we suggest that the sequence variants in the genes coding for inflammatory mediators may contribute to the clinical variability of CMT.
13

A novel homozygous mutation in the WNK1/HSN2 gene causing hereditary sensory neuropathy type 2

71%
Potulska-Chromik A., Kabzinska D., Lipowska M., Kostera-Pruszczyk A., Kochanski A.
Acta Biochimica Polonica
|
2012
|
tom 59
|
nr 3
 Hereditary sensory and autonomic neuropathy type 2 is a rare disorder caused by recessive mutations in the WNK1/HSN2 gene located on chromosome 12p13.33. Phenotype of the patients is characterized by severe sensory loss affecting all sensory modalities. We report a novel homozygous Lys179fsX182 (HSN2); Lys965fsX968 (WNK1/HSN2) mutation causing an early childhood onset hereditary sensory and autonomic neuropathy type 2, with acromutilations in upper and lower limbs, and autonomic dysfunction. To the best of our knowledge this is the first genetically proven case of hereditary sensory and autonomic neuropathy type 2 originating from East Europe.
14

A novel TPM2 gene splice-site mutation causes severe congenital myopathy with arthrogryposis and dysmorphic features

71%
Mroczek M., Kabzinska D., Chrzanowska K. H., Pronicki M., Kochanski A.
Journal of Applied Genetics
|
2017
|
tom 58
|
nr 2
15

A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation

71%
Kabzinska D., Kotruchow K., Cegielska J., Hausmanowa-Petrusewicz I., Kochanski A.
Acta Biochimica Polonica
|
2014
|
tom 61
|
nr 4
16

Dysmyelinating and demyelinating Charcot-Marie-Tooth disease associated with two myelin protein zero gene mutations

61%
Drac H., Kabzinska D., Moszynska I., Strugalska-Cynowska H., Hausmanowa-Petrusewicz I., Kochanski A.
Journal of Applied Genetics
|
2011
|
tom 52
|
nr 2
Mutations in the myelin protein zero (MPZ) gene are the third most frequent cause of hereditary motor and sensory neuropathies (HMSN), also called Charcot–Marie–Tooth disorders (CMT). Only in case of recurrent mutations occurring in the MPZ gene is it possible to draw phenotype–genotype correlations essential for establishing the prognosis and outcomes of CMT1. We have surveyed a cohort of 67 Polish patients from CMT families with demyelinating neuropathy for mutations in the MPZ gene. In this study, we report two CMT families in which the Ile135Thr and Pro132Leu mutations have been identified for the MPZ gene. These MPZ gene mutations had not been identified hitherto in the Polish population. The Pro132Leu mutation segregates with a severe early-onset dysmyelinating–hypomyelinating neuropathy, whereas the Ile135Thr substitution is associated with the classical phenotype of CMT1. To the best of our knowledge, we present here, for the first time, morphological data obtained in two sural nerve biopsies pointing to a hypomyelination–dysmyelination process in a family harboring the Pro132Leu mutation in the MPZ gene.
17

Comparison between the Polish population and European populations on the basis of mitochondrial morphs and haplogroups

61%
Piechota J., Tonska K., Nowak M., Kabzinska D., Lorenc A., Bartnik E.
Acta Biochimica Polonica
|
2004
|
tom 51
|
nr 4
Polymorphisms in mitochondrial DNA (mtDNA) were analyzed in 152 samples from the Polish population using restriction enzymes AvaI, BamHI, HaeII, HpaI and PstI. Additionally, each sample was classified into the appropriate haplogroup. When required, appropriate fragments were sequenced to establish the exact poly­morphic sites. We found one new morph for PstI and six new morphs for AvaII. Some detected morphs have previously been described as population specific morphs in different regions of the world. All polymorphisms were classified into 31 different haplotypes. 21 of them were detected in single individuals. The Polish population was compared with other populations from different regions. Moreover, we have ob­tained evidence for mutation hot spots in the mtDNA coding region. Our results indi­cate that AvaII morph and haplogroup composition of the Polish population is simi­lar to other European populations and has a distribution typical for this part of the world. However, statistically significant differences in haplogroup composition were found between the Polish population and Italian and Finnish populations.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.