LIVIVO - Search results -

Search results

Result 1 - 10 of total 10

Search options

Article ; Online: Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome.

Nalini, Atchayaram / Pandraud, Amelie / Mok, Kin / Houlden, Henry

2013 Volume 334, Issue 1-2, Page(s) 119–122

Abstract: Introduction: Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of ... ...

Abstract	Introduction: Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown-Vialetto-Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio-Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively). Methods and results: We describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10. Conclusions: These data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors.
MeSH term(s)	Adolescent ; Adult ; Bulbar Palsy, Progressive/genetics ; Child ; Female ; Hearing Loss, Sensorineural/genetics ; Humans ; India ; Male ; Membrane Transport Proteins/genetics ; Motor Neuron Disease/genetics ; Mutation ; Pedigree ; Receptors, G-Protein-Coupled/genetics
Chemical Substances	Membrane Transport Proteins ; Receptors, G-Protein-Coupled ; SLC52A2 protein, human ; SLC52A3 protein, human
Language	English
Publishing date	2013-08-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2013.08.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 308: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease.

Kalmar, Bernadett / Innes, Amy / Wanisch, Klaus / Kolaszynska, Alicia Koyen / Pandraud, Amelie / Kelly, Gavin / Abramov, Andrey Y / Reilly, Mary M / Schiavo, Giampietro / Greensmith, Linda

Human molecular genetics

2017 Volume 26, Issue 17, Page(s) 3313–3326

Abstract: Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been ... ...

Abstract	Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease.
MeSH term(s)	Animals ; Axonal Transport/genetics ; Axonal Transport/physiology ; Axons/metabolism ; Cell Culture Techniques ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/metabolism ; HSP27 Heat-Shock Proteins/genetics ; HSP27 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Mice ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondria/pathology ; Motor Neurons/metabolism ; Mutation ; Neoplasm Proteins/genetics
Chemical Substances	HSP27 Heat-Shock Proteins ; Heat-Shock Proteins ; Hspb2 protein, mouse ; Neoplasm Proteins
Language	English
Publishing date	2017-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddx216
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Novel peripheral myelin protein 22 (PMP22) micromutations associated with variable phenotypes in Greek patients with Charcot-Marie-Tooth disease.

Koutsis, Georgios / Pandraud, Amelie / Polke, James M / Wood, Nicholas W / Panas, Marios / Karadima, Georgia / Houlden, Henry

Brain : a journal of neurology

2012 Volume 135, Issue Pt 8, Page(s) e217, 1–6; author reply e218, 1–2

MeSH term(s)	Female ; Hereditary Central Nervous System Demyelinating Diseases/genetics ; Humans ; Male ; Mutation ; Myelin Proteins/genetics
Chemical Substances	Myelin Proteins
Language	English
Publishing date	2012-03-01
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/aws034
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

Bryson, J Barney / Hobbs, Carl / Parsons, Michael J / Bosch, Karen D / Pandraud, Amelie / Walsh, Frank S / Doherty, Patrick / Greensmith, Linda

Human molecular genetics

2012 Volume 21, Issue 17, Page(s) 3871–3882

Abstract: In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres ... ...

Abstract	In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS. We have further characterized this response in SOD1(G93A) mice and also revealed elevated levels of β-amyloid (Aβ) peptides in the SOD1(G93A) spinal cord, which were predominantly localized within motor neurons and their surrounding glial cells. We therefore examined the effect of genetic ablation of APP on disease progression in SOD1(G93A) mice, which significantly improved multiple disease parameters, including innervation, motor function, muscle contractile characteristics, motor unit and motor neuron survival. These results therefore strongly suggest that APP actively contributes to SOD1(G93A)-mediated pathology. Together with observations from ALS cases, this study indicates that APP may contribute to human ALS pathology.
MeSH term(s)	Amino Acid Substitution/genetics ; Amyloid beta-Protein Precursor/metabolism ; Amyotrophic Lateral Sclerosis/enzymology ; Amyotrophic Lateral Sclerosis/pathology ; Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Atrophy ; Body Weight ; Cell Survival ; Crosses, Genetic ; Disease Models, Animal ; Female ; Humans ; Longevity ; Male ; Mice ; Mice, Knockout ; Motor Activity ; Motor Neurons/metabolism ; Motor Neurons/pathology ; Muscle Denervation ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/pathology ; Neuromuscular Junction/metabolism ; Neuromuscular Junction/pathology ; Neuromuscular Junction/physiopathology ; Protein Processing, Post-Translational ; Solubility ; Spinal Cord/pathology ; Spinal Cord/physiopathology ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1 ; Up-Regulation
Chemical Substances	Amyloid beta-Protein Precursor ; SOD1 protein, human ; Sod1 protein, mouse (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1)
Language	English
Publishing date	2012-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/dds215
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Severe Dejerine-Sottas disease with respiratory failure and dysmorphic features in association with a PMP22 point mutation and a 3q23 microdeletion.

Voermans, Nicol C / Kleefstra, Tjitske / Gabreëls-Festen, Anneke A / Faas, Brigitte H W / Kamsteeg, Erik-Jan / Houlden, Henry / Laurá, Matilde / Polke, James M / Pandraud, Amelie / van Ruissen, Fred / van Engelen, Baziel G / Reilly, Mary M

Journal of the peripheral nervous system : JPNS

2012 Volume 17, Issue 2, Page(s) 223–225

MeSH term(s)	Abnormalities, Multiple/genetics ; Chromosomes, Human, Pair 3/genetics ; Female ; Gene Deletion ; Hereditary Sensory and Motor Neuropathy/genetics ; Hereditary Sensory and Motor Neuropathy/pathology ; Humans ; Myelin Proteins/genetics ; Point Mutation ; Respiratory Insufficiency/genetics ; Young Adult
Chemical Substances	Myelin Proteins ; PMP22 protein, human
Language	English
Publishing date	2012-06-26
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	1364009-4
ISSN	1529-8027 ; 1085-9489
ISSN (online)	1529-8027
ISSN	1085-9489
DOI	10.1111/j.1529-8027.2012.00402.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5106: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: A 6.4 Mb duplication of the α-synuclein locus causing frontotemporal dementia and Parkinsonism: phenotype-genotype correlations.

Kara, Eleanna / Kiely, Aoife P / Proukakis, Christos / Giffin, Nicola / Love, Seth / Hehir, Jason / Rantell, Khadija / Pandraud, Amelie / Hernandez, Dena G / Nacheva, Elizabeth / Pittman, Alan M / Nalls, Mike A / Singleton, Andrew B / Revesz, Tamas / Bhatia, Kailash P / Quinn, Niall / Hardy, John / Holton, Janice L / Houlden, Henry

JAMA neurology

2014 Volume 71, Issue 9, Page(s) 1162–1171

Abstract: Importance: α-Synuclein (SNCA) locus duplications are associated with variable clinical features and reduced penetrance but the reasons underlying this variability are unknown.: Objectives: To report a novel family carrying a heterozygous 6.4 Mb ... ...

Abstract	Importance: α-Synuclein (SNCA) locus duplications are associated with variable clinical features and reduced penetrance but the reasons underlying this variability are unknown. Objectives: To report a novel family carrying a heterozygous 6.4 Mb duplication of the SNCA locus with an atypical clinical presentation strongly reminiscent of frontotemporal dementia and late-onset pallidopyramidal syndromes and study phenotype-genotype correlations in SNCA locus duplications. Design, setting, and participants: We report the clinical and neuropathologic features of a family carrying a 6.4 Mb duplication of the SNCA locus. To identify candidate disease modifiers, we completed a genetic analysis of the family and conducted statistical analysis on previously published cases carrying SNCA locus duplications using regression modeling with robust standard errors to account for clustering at the family level. Main outcomes and measures: We assessed whether length of the SNCA locus duplication influences disease penetrance and severity and whether extraduplication factors have a disease-modifying role. Results: We identified a large 6.4 Mb duplication of the SNCA locus in this family. Neuropathological analysis showed extensive α-synuclein pathology with minimal phospho-tau pathology. Genetic analysis showed an increased burden of Parkinson disease-related risk factors and the disease-predisposing H1/H1 microtubule-associated protein tau haplotype. Statistical analysis of previously published cases suggested there is a trend toward increasing disease severity and disease penetrance with increasing duplication size. The corresponding odds ratios from the univariable analyses were 1.17 (95% CI, 0.81-1.68) and 1.34 (95% CI, 0.78-2.31), respectively. Sex was significantly associated with both disease risk and severity; men compared with women had increased disease risk and severity and the corresponding odds ratios from the univariable analyses were 8.36 (95% CI, 1.97-35.42) and 5.55 (95% CI, 1.39-22.22), respectively. Conclusions and relevance: These findings further expand the phenotypic spectrum of SNCA locus duplications. Increased dosage of genes located within the duplicated region probably cannot increase disease risk and disease severity without the contribution of additional risk factors. Identification of disease modifiers accounting for the substantial phenotypic heterogeneity of patients with SNCA locus duplications could provide insight into molecular events involved in α-synuclein aggregation.
MeSH term(s)	Age of Onset ; Brain/metabolism ; Brain/pathology ; Female ; Frontotemporal Dementia/genetics ; Frontotemporal Dementia/pathology ; Frontotemporal Dementia/physiopathology ; Gene Dosage ; Gene Duplication/genetics ; Genetic Association Studies/methods ; Genetic Loci/genetics ; Genetic Predisposition to Disease ; Humans ; Microsatellite Repeats/genetics ; Middle Aged ; Odds Ratio ; Parkinsonian Disorders/genetics ; Parkinsonian Disorders/pathology ; Parkinsonian Disorders/physiopathology ; Pedigree ; Penetrance ; Risk Factors ; Severity of Illness Index ; Sex Factors ; alpha-Synuclein/genetics
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2014-07-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2014.994
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.191: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

Manole, Andreea / Jaunmuktane, Zane / Hargreaves, Iain / Ludtmann, Marthe H R / Salpietro, Vincenzo / Bello, Oscar D / Pope, Simon / Pandraud, Amelie / Horga, Alejandro / Scalco, Renata S / Li, Abi / Ashokkumar, Balasubramaniem / Lourenço, Charles M / Heales, Simon / Horvath, Rita / Chinnery, Patrick F / Toro, Camilo / Singleton, Andrew B / Jacques, Thomas S /

Abramov, Andrey Y / Muntoni, Francesco / Hanna, Michael G / Reilly, Mary M / Revesz, Tamas / Kullmann, Dimitri M / Jepson, James E C / Houlden, Henry

Brain : a journal of neurology

2017 Volume 140, Issue 11, Page(s) 2820–2837

Abstract: Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin ... ...

Abstract	Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy.
MeSH term(s)	Adolescent ; Animals ; Atrophy ; Brain/pathology ; Brain/ultrastructure ; Bulbar Palsy, Progressive/genetics ; Bulbar Palsy, Progressive/metabolism ; Bulbar Palsy, Progressive/pathology ; Child ; Child, Preschool ; Citrate (si)-Synthase/metabolism ; Drosophila melanogaster ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Electron Transport Complex III/metabolism ; Female ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; Hearing Loss, Sensorineural/genetics ; Hearing Loss, Sensorineural/metabolism ; Hearing Loss, Sensorineural/pathology ; Humans ; In Vitro Techniques ; Infant ; Locomotion/genetics ; Longevity/genetics ; Male ; Membrane Transport Proteins/genetics ; Microscopy, Electron ; Neural Pathways ; Receptors, G-Protein-Coupled/genetics ; Riboflavin ; Spinal Cord/pathology ; Spinocerebellar Tracts/pathology ; Spinothalamic Tracts/pathology ; Young Adult
Chemical Substances	Membrane Transport Proteins ; Receptors, G-Protein-Coupled ; SLC52A2 protein, human ; SLC52A3 protein, human ; Electron Transport Complex II (EC 1.3.5.1) ; Citrate (si)-Synthase (EC 2.3.3.1) ; Electron Transport Complex I (EC 7.1.1.2) ; Electron Transport Complex III (EC 7.1.1.8) ; Riboflavin (TLM2976OFR)
Language	English
Publishing date	2017-10-20
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awx231
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease.

Johnson, Janel O / Gibbs, J Raphael / Megarbane, Andre / Urtizberea, J Andoni / Hernandez, Dena G / Foley, A Reghan / Arepalli, Sampath / Pandraud, Amelie / Simón-Sánchez, Javier / Clayton, Peter / Reilly, Mary M / Muntoni, Francesco / Abramzon, Yevgeniya / Houlden, Henry / Singleton, Andrew B

Brain : a journal of neurology

2012 Volume 135, Issue Pt 9, Page(s) 2875–2882

Abstract: Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly ... ...

Abstract	Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown-Vialetto-Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown-Vialetto-Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown-Vialetto-Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results.
MeSH term(s)	Alleles ; Bulbar Palsy, Progressive/genetics ; Child ; Child, Preschool ; Exome ; Female ; Gene Frequency ; Genotype ; Hearing Loss, Sensorineural/genetics ; Humans ; Male ; Motor Neuron Disease/genetics ; Mutation ; Pedigree ; Polymorphism, Single Nucleotide ; Receptors, G-Protein-Coupled/genetics
Chemical Substances	Receptors, G-Protein-Coupled ; SLC52A2 protein, human
Language	English
Publishing date	2012-06-26
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/aws161
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.

Murphy, Sinead M / Laura, Matilde / Fawcett, Katherine / Pandraud, Amelie / Liu, Yo-Tsen / Davidson, Gabrielle L / Rossor, Alexander M / Polke, James M / Castleman, Victoria / Manji, Hadi / Lunn, Michael P T / Bull, Karen / Ramdharry, Gita / Davis, Mary / Blake, Julian C / Houlden, Henry / Reilly, Mary M

Journal of neurology, neurosurgery, and psychiatry

2012 Volume 83, Issue 7, Page(s) 706–710

Abstract: Background: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large ...

Abstract	Background: Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice. Methods: The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population. Results: A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare. Conclusion: Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximise the chance of reaching a molecular diagnosis.
MeSH term(s)	Charcot-Marie-Tooth Disease/classification ; Charcot-Marie-Tooth Disease/diagnosis ; Charcot-Marie-Tooth Disease/genetics ; Cohort Studies ; Female ; Gene Frequency/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Testing/methods ; Genetic Testing/standards ; Humans ; Male ; Mutation/genetics ; Practice Guidelines as Topic
Language	English
Publishing date	2012-05-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2012-302451
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.93: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2.

Foley, A Reghan / Menezes, Manoj P / Pandraud, Amelie / Gonzalez, Michael A / Al-Odaib, Ahmad / Abrams, Alexander J / Sugano, Kumiko / Yonezawa, Atsushi / Manzur, Adnan Y / Burns, Joshua / Hughes, Imelda / McCullagh, B Gary / Jungbluth, Heinz / Lim, Ming J / Lin, Jean-Pierre / Megarbane, Andre / Urtizberea, J Andoni / Shah, Ayaz H / Antony, Jayne /

Webster, Richard / Broomfield, Alexander / Ng, Joanne / Mathew, Ann A / O'Byrne, James J / Forman, Eva / Scoto, Mariacristina / Prasad, Manish / O'Brien, Katherine / Olpin, Simon / Oppenheim, Marcus / Hargreaves, Iain / Land, John M / Wang, Min X / Carpenter, Kevin / Horvath, Rita / Straub, Volker / Lek, Monkol / Gold, Wendy / Farrell, Michael O / Brandner, Sebastian / Phadke, Rahul / Matsubara, Kazuo / McGarvey, Michael L / Scherer, Steven S / Baxter, Peter S / King, Mary D / Clayton, Peter / Rahman, Shamima / Reilly, Mary M / Ouvrier, Robert A / Christodoulou, John / Züchner, Stephan / Muntoni, Francesco / Houlden, Henry

Brain : a journal of neurology

2013 Volume 137, Issue Pt 1, Page(s) 44–56

Abstract: Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive ... ...

Abstract	Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.
MeSH term(s)	Adolescent ; Brain/pathology ; Bulbar Palsy, Progressive/drug therapy ; Bulbar Palsy, Progressive/genetics ; Carnitine/analogs & derivatives ; Carnitine/blood ; Child ; Child, Preschool ; Exome/genetics ; Female ; Genotype ; Hearing Loss, Sensorineural/drug therapy ; Hearing Loss, Sensorineural/genetics ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Microarray Analysis ; Motor Neuron Disease/physiopathology ; Mutation/genetics ; Neurologic Examination ; Pedigree ; RNA/biosynthesis ; RNA/genetics ; Receptors, G-Protein-Coupled/genetics ; Riboflavin/therapeutic use ; Sequence Analysis, DNA ; Sural Nerve/pathology ; Vitamins/therapeutic use ; Young Adult
Chemical Substances	Receptors, G-Protein-Coupled ; SLC52A2 protein, human ; Vitamins ; acylcarnitine ; RNA (63231-63-0) ; Carnitine (S7UI8SM58A) ; Riboflavin (TLM2976OFR)
Language	English
Publishing date	2013-11-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awt315
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito