The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Janel O Johnson - One of the best experts on this subject based on the ideXlab platform.
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exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
Brain, 2012Co-Authors: Andre Megarbane, Janel O Johnson, Raphael J Gibbs, Andoni J Urtizberea, Dena G Hernandez, Reghan A Foley, Sampath ArepalliAbstract: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. * Abbreviations : MADD : multiple acyl-CoA dehydrogenase deficiency SNP : single-nucleotide polymorphism
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exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
Brain, 2012Co-Authors: Andre Megarbane, Janel O Johnson, Raphael J Gibbs, Andoni J Urtizberea, Dena G Hernandez, Reghan A Foley, Sampath ArepalliAbstract: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.
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exome sequencing in brown vialetto van Laere Syndrome
American Journal of Human Genetics, 2010Co-Authors: Henry Houlden, Janel O Johnson, Raphael J Gibbs, Lionel Van Maldergem, Andrew B SingletonAbstract:To the Editor: Brown-Vialetto-Van Laere Syndrome (BVVL [MIM 211530]) is a rare, progressive, childhood neurodegenerative disease that is characterized by pontobulbar palsy, sensorineural hearing loss, and respiratory problems. BVVL is clinically heterogeneous, presenting as early as the neonatal period and as late as the third decade of life.1 BVVL has a prominent familial component, consistent with an autosomal-recessive mode of inheritance, in all but one family reported. The genetic cause of BVVL was until recently unknown; therefore, we read with interest the recent article by Green and colleagues that described mutations of C20orf54 (MIM 613350) as the underlying cause of BVVL.
Raphael J Gibbs - One of the best experts on this subject based on the ideXlab platform.
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exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
Brain, 2012Co-Authors: Andre Megarbane, Janel O Johnson, Raphael J Gibbs, Andoni J Urtizberea, Dena G Hernandez, Reghan A Foley, Sampath ArepalliAbstract: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. * Abbreviations : MADD : multiple acyl-CoA dehydrogenase deficiency SNP : single-nucleotide polymorphism
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exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
Brain, 2012Co-Authors: Andre Megarbane, Janel O Johnson, Raphael J Gibbs, Andoni J Urtizberea, Dena G Hernandez, Reghan A Foley, Sampath ArepalliAbstract: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.
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exome sequencing in brown vialetto van Laere Syndrome
American Journal of Human Genetics, 2010Co-Authors: Henry Houlden, Janel O Johnson, Raphael J Gibbs, Lionel Van Maldergem, Andrew B SingletonAbstract:To the Editor: Brown-Vialetto-Van Laere Syndrome (BVVL [MIM 211530]) is a rare, progressive, childhood neurodegenerative disease that is characterized by pontobulbar palsy, sensorineural hearing loss, and respiratory problems. BVVL is clinically heterogeneous, presenting as early as the neonatal period and as late as the third decade of life.1 BVVL has a prominent familial component, consistent with an autosomal-recessive mode of inheritance, in all but one family reported. The genetic cause of BVVL was until recently unknown; therefore, we read with interest the recent article by Green and colleagues that described mutations of C20orf54 (MIM 613350) as the underlying cause of BVVL.
Hans R. Waterham - One of the best experts on this subject based on the ideXlab platform.
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the brown vialetto van Laere and fazio londe Syndrome revisited natural history genetics treatment and future perspectives
Orphanet Journal of Rare Diseases, 2012Co-Authors: Annet M. Bosch, Nico G. G. M. Abeling, Lodewijk Ijlst, Hans R. Waterham, Kevin Stroek, Ronald J A WandersAbstract:The Brown-Vialetto-Van Laere Syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe Syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL Syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL Syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months.
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brown vialetto van Laere Syndrome a riboflavin unresponsive patient with a novel mutation in the c20orf54 gene
Pediatric Neurology, 2012Co-Authors: Anne Koy, Hans R. Waterham, Frank Pillekamp, Thomas Hoehn, Dirk Klee, Ertan Mayatepek, Birgit AssmannAbstract:Abstract Brown-Vialetto-Van Laere Syndrome (Online Mendelian Inheritance in Man number 211530) is a neurodegenerative disorder characterized by pontobulbar palsy affecting cranial nerves (mainly VII-XII). Sensorineural deafness is often the leading sign, followed by other neurologic signs. Inheritance is often autosomal recessive, with mutations in the C20orf54 gene (Online Mendelian Inheritance in Man number 613350). Three previous patients with mutations in the C20orf54 gene and clinical signs of Brown-Vialetto-Van Laere or Fazio-Londe Syndrome revealed a metabolic profile suggesting a multiple acyl-coenzyme A dehydrogenase defect. They benefited from riboflavin. We describe a 3-year-old girl with early-onset Brown-Vialetto-Van Laere Syndrome and a novel mutation in the C20orf54 gene (c.989G>T). On T 2 -weighted imaging, increased signal intensity of the vestibular nuclei bilaterally, the pedunculus cerebellaris superior and the central tegmental tract were observed during acute clinical deterioration. Her metabolic profile was normal. Trials with steroids, immunoglobulins, and riboflavin produced no effect. The patient recovered slowly during subsequent months, with residual deficits. Brown-Vialetto-Van Laere Syndrome should be considered in patients with sensorineural hearing loss and pontobulbar palsy. Patients should be screened for riboflavin deficiency and a therapy with riboflavin may provide effective treatment in some affected patients.
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Brown-Vialetto-Van Laere and Fazio Londe Syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment
Journal of Inherited Metabolic Disease, 2011Co-Authors: Annet M. Bosch, Marinus Duran, Nico G. G. M. Abeling, Lodewijk Ijlst, Hennie Knoester, Alida E. M. Stroomer, Gepke Visser, Frits A. Wijburg, Hans R. WaterhamAbstract:We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid Syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere Syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere Syndrome as well as for the Fazio Londe Syndrome which is considered to be the same disease entity without the deafness.
Henry Houlden - One of the best experts on this subject based on the ideXlab platform.
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madras motor neuron disease mmnd is distinct from the riboflavin transporter genetic defects that cause brown vialetto van Laere Syndrome
Journal of the Neurological Sciences, 2013Co-Authors: A Nalini, Amelie Pandraud, Kin Y Mok, Henry HouldenAbstract: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).
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exome sequencing in brown vialetto van Laere Syndrome
American Journal of Human Genetics, 2010Co-Authors: Henry Houlden, Janel O Johnson, Raphael J Gibbs, Lionel Van Maldergem, Andrew B SingletonAbstract:To the Editor: Brown-Vialetto-Van Laere Syndrome (BVVL [MIM 211530]) is a rare, progressive, childhood neurodegenerative disease that is characterized by pontobulbar palsy, sensorineural hearing loss, and respiratory problems. BVVL is clinically heterogeneous, presenting as early as the neonatal period and as late as the third decade of life.1 BVVL has a prominent familial component, consistent with an autosomal-recessive mode of inheritance, in all but one family reported. The genetic cause of BVVL was until recently unknown; therefore, we read with interest the recent article by Green and colleagues that described mutations of C20orf54 (MIM 613350) as the underlying cause of BVVL.
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brown vialetto van Laere Syndrome a ponto bulbar palsy with deafness is caused by mutations in c20orf54
American Journal of Human Genetics, 2010Co-Authors: Peter M Green, Matthew Wiseman, Yanick J Crow, Henry Houlden, Shelley Riphagen, Jeanpierre Lin, Lucy F Raymond, Anne Marie Childs, Eamonn Sheridan, Sian E EdwardsAbstract:Brown-Vialetto-Van Laere Syndrome is a rare neurological disorder with a variable age at onset and clinical course. The key features are progressive ponto-bulbar palsy and bilateral sensorineural deafness. A complex neurological phenotype with a mixed picture of upper and lower motor neuron involvement reminiscent of amyotrophic lateral sclerosis evolves with disease progression. We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families.
C Shaw - One of the best experts on this subject based on the ideXlab platform.
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remarkable motor recovery after riboflavin therapy in adult onset brown vialetto van Laere Syndrome
Practical Neurology, 2017Co-Authors: James Bashford, Fahmida A Chowdhury, C ShawAbstract:The clinical diagnosis of Brown—Vialetto—Van Laere Syndrome in this woman with rapidly progressive pontobulbar palsy led to empirical high-dose oral riboflavin (1200 mg/day) therapy. This resulted in a dramatic improvement in her motor function from being anarthric, dysphagic, tetraparetic and in ventilatory failure to living independently with mild dysarthria and distal limb weakness. DNA sequencing of the SLC52A3 gene found compound heterozygous C-terminus mutations, V413A1/D461Y, consistent with recent reports of mutations within the riboflavin transporter genes ( SLC52A2 and SLC52A3 ) in this condition. Early diagnosis and empirical riboflavin therapy can lead to major motor recovery in this condition, that can be sustained with long-term maintenance therapy.
