Tommaso Schirinzi, Gessica Vasco, Ginevra Zanni, Sara Petrillo, Fiorella Piemonte, Enrico Castelli, Enrico Silvio Bertini, Clinical Biochemistry, Available online 2 February 2018, ISSN 0009-9120, doi:10.1016/j.clinbiochem.2018.01.022.
Serum UA levels resulted significantly higher in FRDA than CTL, independently from age, gender and BMI. At the cut-off value of 4.45 mg/dl, serum UA discriminates FRDA from CTL with >70% of sensitivity and >60% of specificity. No correlations emerged with clinical data. Contrarily to other neurodegenerative diseases, in FRDA, we observed an independent increase of serum UA content. Taking in account previous experimental findings, we speculate that such a finding may result from biochemical impairment induced by the genetic defect, acting as a sort of compensatory antioxidant defense although proper dedicated studies are mandatory. This preliminary report focuses UA as a potential biomarker for FRDA and encourages further studies on novel therapeutic strategies.
Sunday, February 4, 2018
Differential gene expression analysis reveals pathway based functional association of dysregulated genes in Friedreich’s ataxia
H.N. Singh, V. Swarup, A.K. Srivastava, Parkinsonism & Related Disorders, Volume 46, Supplement 2, January 2018, Page e34, ISSN 1353-8020, doi:10.1016/j.parkreldis.2017.11.112.
A total of 3594 different gene-sets were identified and analyzed in the expression analysis. Out of 3594 gene-sets, 2009 were up-regulated in
the control phenotype and 1585 genes were up-regulated in FRDA conditions.
A total of 3594 different gene-sets were identified and analyzed in the expression analysis. Out of 3594 gene-sets, 2009 were up-regulated in
the control phenotype and 1585 genes were up-regulated in FRDA conditions.
Sequence-specific DNA Binding Pyrrole–Imidazole Polyamides and Their Applications
Yusuke Kawamoto, Toshikazu Bando, Hiroshi Sugiyama, Bioorganic & Medicinal Chemistry, Available online 1 February 2018, ISSN 0968-0896, doi:10.1016/j.bmc.2018.01.026.
Pyrrole–imidazole polyamides (Py–Im polyamides) are cell-permeable compounds that bind to the minor groove of double-stranded DNA in a sequence-specific manner without causing denaturation of the DNA. These compounds can be used to control gene expression and to stain specific sequences in cells. Here, we review the history, structural variations, and functional investigations of Py–Im polyamides.
Pyrrole–imidazole polyamides (Py–Im polyamides) are cell-permeable compounds that bind to the minor groove of double-stranded DNA in a sequence-specific manner without causing denaturation of the DNA. These compounds can be used to control gene expression and to stain specific sequences in cells. Here, we review the history, structural variations, and functional investigations of Py–Im polyamides.
Prevalence of hemochromatosis (HFE) gene mutations in Friedreich’s Ataxia patients and peripheral neuropathy
I. Singh, S. Shakya, R.K. Singh, V. Goyal, A.K. Srivastava, Parkinsonism & Related Disorders, Volume 46, Supplement 2, January 2018, Page e4, ISSN 1353-8020, doi:10.1016/j.parkreldis.2017.11.014.
Allele frequency of p.H63D mutation was statistically higher (p-value 0.04) in cases than controls. Peripheral neuropathy in our patients
correlated with p.H63D (p-value 0.038)
Allele frequency of p.H63D mutation was statistically higher (p-value 0.04) in cases than controls. Peripheral neuropathy in our patients
correlated with p.H63D (p-value 0.038)
Friday, February 2, 2018
A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)
Weihua Meng, Mark J. Adams, Harry L. Hebert, Ian J. Deary, Andrew M. McIntosh, Blair H. Smith, EBioMedicine, Available online 31 January 2018, ISSN 2352-3964, doi:10.1016/j.ebiom.2018.01.023.
Loci associated with broadly-defined headache: Gene FXN, Chromosome 9, Lead SNP rs4596713, P 2.30 × 10− 8, Effective allele T, Minor allele frequency 0.41, Beta− 0.0078, standard error 0.0014.
Loci associated with broadly-defined headache: Gene FXN, Chromosome 9, Lead SNP rs4596713, P 2.30 × 10− 8, Effective allele T, Minor allele frequency 0.41, Beta− 0.0078, standard error 0.0014.
Neurology Measures in FA Children
February 1, 2018. ClinicalTrials.gov identifier (NCT number): NCT03418740
The purpose of this study is to identify ways to follow progression of Friedreich's Ataxia (FA) and be able to measure changes over time in children with FA. Participants will have biannual visits to observe how the disease progresses over time and determine the rate of progression.
The purpose of this study is to identify ways to follow progression of Friedreich's Ataxia (FA) and be able to measure changes over time in children with FA. Participants will have biannual visits to observe how the disease progresses over time and determine the rate of progression.
Wednesday, January 31, 2018
Common drug review recommendations for orphan drugs in Canada: basis of recommendations and comparison with similar reviews in Quebec, Australia, Scotland and New Zealand
John I. McCormick, L. Diana Berescu and Nabil Tadros; Orphanet Journal of Rare Diseases201813:27 doi:10.1186/s13023-018-0759-9
The positive recommendation rate for CDR reviews of orphan drugs was highest when both clinical and price parameters formed the basis of the assessment. However, there was a change in CDR review policies in 2016, with a dramatic increase in the number of positive recommendations, the majority of which were conditional on a substantial reduction in drug price. This change in CDR recommendations is reflected in the expanded criteria and conditions of drug reimbursement outlined in CADTH’s March 2016 recommendation framework. However, it remains to be seen if this represents a permanent change in how CDR reviews orphan drugs and if this will result in wider and more timely provincial access for orphan drugs for patients throughout Canada.
The positive recommendation rate for CDR reviews of orphan drugs was highest when both clinical and price parameters formed the basis of the assessment. However, there was a change in CDR review policies in 2016, with a dramatic increase in the number of positive recommendations, the majority of which were conditional on a substantial reduction in drug price. This change in CDR recommendations is reflected in the expanded criteria and conditions of drug reimbursement outlined in CADTH’s March 2016 recommendation framework. However, it remains to be seen if this represents a permanent change in how CDR reviews orphan drugs and if this will result in wider and more timely provincial access for orphan drugs for patients throughout Canada.
Monday, January 29, 2018
Late onset friedreich ataxia presented with spastic paraparesis
G. PSIMMENOS, N. Grigoriadis, D. Parisis, T. Afrantou, P. Ioannidis; Thessaloniki/GR; (Poster POD416) EAN Congress 2017 in Amsterdam
We report two cases , a 56 year old male patient and a 29 year old female patient. In both cases examination revealed typical clinical symptoms of the disease such as gait-limb ataxia , impaired tandem gait, severe swaying on testing for Romberg sign. There was no history of weakness or numbness. The uncommon findings in both of them were the exaggerated deep tendon reflexes and that the symptoms appeared at such an advanced age(>26 years old).That was the reason why both patients initially underwent genetic testing for other genetic disorders(spinocerebellar ataxia SCA). Genetic testing disclosed expanded GAA repeat length of FTX gene confirming a diagnosis of FA.
These cases highlight that the existence of increased tendon reflexes, although unusual is not incompatible with FA and thus should not prevent the clinician to consider it as a possible diagnosis when the rest clinical picture, the personal-family history and the neurological signs are in keeping with diagnosis of FA
We report two cases , a 56 year old male patient and a 29 year old female patient. In both cases examination revealed typical clinical symptoms of the disease such as gait-limb ataxia , impaired tandem gait, severe swaying on testing for Romberg sign. There was no history of weakness or numbness. The uncommon findings in both of them were the exaggerated deep tendon reflexes and that the symptoms appeared at such an advanced age(>26 years old).That was the reason why both patients initially underwent genetic testing for other genetic disorders(spinocerebellar ataxia SCA). Genetic testing disclosed expanded GAA repeat length of FTX gene confirming a diagnosis of FA.
These cases highlight that the existence of increased tendon reflexes, although unusual is not incompatible with FA and thus should not prevent the clinician to consider it as a possible diagnosis when the rest clinical picture, the personal-family history and the neurological signs are in keeping with diagnosis of FA
Early onset Friedreich Ataxia without cardiomyopathy
O. Rujan, I. BURAGA, A. Enachi, I. Ionescu, C. Baetu; Bucharest/RO; (Poster POD163) EAN Congress 2017 in Amsterdam
There is a very important clinical distinction between classic FA and its variants, which consists in the absence of kyphoscoliosis and heart disease (a frequent component) which gives the latter group a better prognosis. Our case shows that an early onset of FA doesn’t necessarily mean the patient will develop cardiomyopathy.
Our patient is a 25 year old female whose symptoms were onset at the age of 3 years old and consisted of ataxia of gait, difficulties in standing steadily and in running. The clinical features progressed slowly and now she presents: gait and limb ataxia, the lower limb reflexes are preserved, Romberg sign is present, a rhythmic tremor of the head and upper limbs (more visible during emotional stress), horizontal nystagmus, the speech is slow, slurred and explosive, pes cavus and hammertoes.
This case has some particularities: the early onset of the symptoms, a very slow progression, the preserved lower limb reflexes and the absence of cardiomyopathy.
There is a very important clinical distinction between classic FA and its variants, which consists in the absence of kyphoscoliosis and heart disease (a frequent component) which gives the latter group a better prognosis. Our case shows that an early onset of FA doesn’t necessarily mean the patient will develop cardiomyopathy.
Our patient is a 25 year old female whose symptoms were onset at the age of 3 years old and consisted of ataxia of gait, difficulties in standing steadily and in running. The clinical features progressed slowly and now she presents: gait and limb ataxia, the lower limb reflexes are preserved, Romberg sign is present, a rhythmic tremor of the head and upper limbs (more visible during emotional stress), horizontal nystagmus, the speech is slow, slurred and explosive, pes cavus and hammertoes.
This case has some particularities: the early onset of the symptoms, a very slow progression, the preserved lower limb reflexes and the absence of cardiomyopathy.
Autosomal-recessive cerebellar ataxias
Brent L. Fogel, Handbook of Clinical Neurology, Elsevier, Volume 147, 2018, Pages 187-209, ISSN 0072-9752, ISBN 9780444632333, Doi:10.1016/B978-0-444-63233-3.00013-0.
The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened the ever-expanding number of causative genes to over 50. In this review, the clinical neurogenetics of the recessive cerebellar ataxias will be discussed, including updates on recently identified novel ataxia genes, advancements in unraveling disease-specific molecular pathogenesis leading to ataxia, potential treatments under development, technologic improvements in diagnostic testing such as clinical exome sequencing, and what the future holds for clinicians and geneticists.
The autosomal-recessive cerebellar ataxias comprise more than half of the known genetic forms of ataxia and represent an extensive group of clinically heterogeneous disorders that can occur at any age but whose onset is typically prior to adulthood. In addition to ataxia, patients often present with polyneuropathy and clinical symptoms outside the nervous system. The most common of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene, but recent advances in genetic analysis have greatly broadened the ever-expanding number of causative genes to over 50. In this review, the clinical neurogenetics of the recessive cerebellar ataxias will be discussed, including updates on recently identified novel ataxia genes, advancements in unraveling disease-specific molecular pathogenesis leading to ataxia, potential treatments under development, technologic improvements in diagnostic testing such as clinical exome sequencing, and what the future holds for clinicians and geneticists.
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