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Dobrila D. Rudnicki - One of the best experts on this subject based on the ideXlab platform.
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junctophilin 3 JPH3 expansion mutations causing huntington disease like 2 hdl2 are common in south african patients with african ancestry and a huntington disease phenotype
American Journal of Medical Genetics, 2015Co-Authors: Amanda Krause, Christopher A. Ross, Claire Mitchell, Fahmida Essop, Susan Tager, James Temlett, Giovanni Stevanin, Dobrila D. RudnickiAbstract:Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. © 2015 Wiley Periodicals, Inc.
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Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.
Annals of Neurology, 2012Co-Authors: Ana I. Seixas, Hiroshi Takeshima, Susan E. Holmes, Amira Pavlovich, Nancy Sachs, Jennifer L. Pruitt, Isabel Silveira, Christopher A. Ross, Russell L. Margolis, Dobrila D. RudnickiAbstract:Objective: Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG orientation, the repeat is located within the alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine. The JPH3 protein product serves to stabilize junctional membrane complexes and regulate neuronal calcium flux. We have previously demonstrated the potential pathogenic properties of JPH3 transcripts containing expanded CUG repeats. The aim of this study was to test the possibility that loss of JPH3 expression or expanded amino acid tracts also contribute to HDL2 pathogenesis. Methods: Transcripts from the HDL2 locus, and their protein products, were examined in HDL2, HD, and control frontal cortex. The effect of loss of JPH3 was examined in mice with partial or complete loss of JPH3. Results: Bidirectional transcription occurs at the HDL2 locus, although expression of antisense transcripts with expanded CAG repeats is limited. Protein products with expanded amino acid tracts were not detected in HDL2 brain. However, JPH3 transcripts and full-length JPH3 protein are decreased in HDL2 brain, and JPH3 hemizygous and null mice exhibit abnormal motor function. Interpretation: Our results suggest that the pathogenic mechanism of HDL2 is multifactorial, involving both a toxic gain of function of JPH3 RNA and a toxic loss of JPH3 expression. Ann Neurol 2012;71:245–257
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an antisense cag repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in huntington s disease like 2 mice
Neuron, 2011Co-Authors: Brian Wilburn, Dobrila D. Rudnicki, Jing Zhao, Tara Murphy Weitz, Yin Cheng, Xiaofeng Gu, Erin R Greiner, Chang Sin Park, Nan WangAbstract:Summary Huntington's disease-like-2 (HDL2) is a phenocopy of Huntington's disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology, and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a promoter at the transgene locus driving the expression of a CAG repeat transcript ( HDL2-CAG ) from the strand antisense to JPH3 , which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 mice, but not control BAC mice, accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2.
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Huntington's disease--like 2 is associated with CUG repeat-containing RNA foci.
Annals of Neurology, 2007Co-Authors: Dobrila D. Rudnicki, Susan E. Holmes, Christopher A. Ross, Charles A. Thornton, Russell L. MargolisAbstract:Objective Huntington's disease–like 2 (HDL2) is caused by a CAG/CTG expansion mutation on chromosome 16q24.3. The repeat falls, in the CTG orientation, within a variably spliced exon of junctophilin-3 (JPH3). The existence of a JPH3 splice variant with the CTG repeat in 3′ untranslated region suggested that transcripts containing an expanded CUG repeat could play a role in the pathogenesis of HDL2, similar to the proposed pathogenic role of expanded CUG repeats in myotonic dystrophy type 1 (DM1). The goal of this study, therefore, was to test the plausibility of an RNA gain-of-function component in the pathogenesis of HDL2. Methods The presence and composition of RNA foci in frontal cortex from HDL2, Huntington's disease, DM1, and control brains were investigated by in situ hybridization and immunohistochemistry. An untranslatable JPH3 transcript containing either a normal or an expanded CUG repeat was engineered and expressed in human embryonic kidney 293 and HT22 cells to further test the toxic RNA hypothesis. The formation of RNA foci and the extent of cell death were quantified. Results RNA foci resembling DM1 foci were detected in neurons in HDL2 cortex and other brain regions. Similar to DM1, the foci colocalize with muscleblind-like protein 1, and nuclear muscleblind-like protein 1 in HDL2 cortical neurons is decreased relative to controls. In cell experiments, expression of a JPH3 transcript with an expanded CUG repeat resulted in the formation of RNA foci that colocalized with muscleblind-like protein 1 and in cell toxicity. Interpretation These results imply that RNA toxicity may contribute to the pathogenesis of HDL2. Ann Neurol 2007;61:272–282
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huntington s disease like 2 can present as chorea acanthocytosis
Neurology, 2003Co-Authors: Ruth H Walker, Susan E. Holmes, Dobrila D. Rudnicki, Astrid Rasmussen, Elisa Alonso, Tohru Matsuura, Tetsuo Ashizawa, B Davidofffeldman, Russell L. MargolisAbstract:To the Editor: We read with interest the article by Walker et al.,1 who report a pedigree of autosomal dominant chorea-acanthocytosis (AD-ChAc) with an expansion of the CTG repeat within junctophilin-3 (JPH3) and without CHAC mutation. Of six patients in other pedigrees, one with Huntington disease-like 2 (HDL2) with peripheral acanthocytosis is also presented. We previously reported a Japanese AD-ChAc pedigree having a frame-shift mutation in the CHAC gene.2 Although the clinical phenotype of the kindred reported by Walker et al. does not completely agree with ours, we undertook genetic analysis for the detection of a CTG/CAG expansion within JPH3 in our pedigree. Genomic DNA was extracted from lymphocytes using standard methods. The coding exon between exon 1 and exon 2B in the JPH3 …
Giovanni Stevanin - One of the best experts on this subject based on the ideXlab platform.
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junctophilin 3 JPH3 expansion mutations causing huntington disease like 2 hdl2 are common in south african patients with african ancestry and a huntington disease phenotype
American Journal of Medical Genetics, 2015Co-Authors: Amanda Krause, Christopher A. Ross, Claire Mitchell, Fahmida Essop, Susan Tager, James Temlett, Giovanni Stevanin, Dobrila D. RudnickiAbstract:Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. © 2015 Wiley Periodicals, Inc.
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huntington s disease like phenotype due to trinucleotide repeat expansions in the tbp and JPH3 genes
Brain, 2003Co-Authors: Giovanni Stevanin, Hiroto Fujigasaki, Annesophie Lebre, Agnes Camuzat, Cecile Jeannequin, Catherine Dode, Junko Takahashi, Robert Bellance, Alexis Brice, Alexandra DurrAbstract:Summary We report a group of 252 patients with a Huntington’s disease-like (HDL) phenotype, including 60 with typical Huntington’s disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington’s disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/ CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington’s disease. Taking into account patients with typical Huntington’s disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
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Huntington’s disease‐like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes
Brain, 2003Co-Authors: Giovanni Stevanin, Hiroto Fujigasaki, Annesophie Lebre, Agnes Camuzat, Cecile Jeannequin, Catherine Dode, Junko Takahashi, Robert Bellance, Alexis BriceAbstract:Summary We report a group of 252 patients with a Huntington’s disease-like (HDL) phenotype, including 60 with typical Huntington’s disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington’s disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/ CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington’s disease. Taking into account patients with typical Huntington’s disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
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A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease–like 2
Nature Genetics, 2001Co-Authors: Susan E. Holmes, Giovanni Stevanin, Alexis Brice, Elizabeth O'hearn, Adam Rosenblatt, Colleen Callahan, Hyon S. Hwang, Roxann G. Ingersoll-ashworth, Adam Fleisher, Nicholas T. PotterAbstract:We recently described a disorder termed Huntington disease–like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W)^ 1 . We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
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A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.
Nature Genetics, 2001Co-Authors: Susan E. Holmes, Giovanni Stevanin, Alexis Brice, Elizabeth O'hearn, Adam Rosenblatt, Colleen Callahan, Hyon S. Hwang, Roxann G. Ingersoll-ashworth, Adam Fleisher, Nicholas T. PotterAbstract:We recently described a disorder termed Huntington disease–like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W)1. We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
Alexis Brice - One of the best experts on this subject based on the ideXlab platform.
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Huntington's disease-like 2 in Brazil--report of 4 patients.
Movement Disorders, 2008Co-Authors: Guilherme Riccioppo Rodrigues, Ruth H Walker, Alexis Brice, Cécile Cazeneuve, Odile Russaouen, Hélio A.g. Teive, Renato P. Munhoz, Nilson Becker, Salmo Raskin, Lineu Cesar WerneckAbstract:: Huntington's disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington's disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent.
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huntington s disease like phenotype due to trinucleotide repeat expansions in the tbp and JPH3 genes
Brain, 2003Co-Authors: Giovanni Stevanin, Hiroto Fujigasaki, Annesophie Lebre, Agnes Camuzat, Cecile Jeannequin, Catherine Dode, Junko Takahashi, Robert Bellance, Alexis Brice, Alexandra DurrAbstract:Summary We report a group of 252 patients with a Huntington’s disease-like (HDL) phenotype, including 60 with typical Huntington’s disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington’s disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/ CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington’s disease. Taking into account patients with typical Huntington’s disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
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Huntington’s disease‐like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes
Brain, 2003Co-Authors: Giovanni Stevanin, Hiroto Fujigasaki, Annesophie Lebre, Agnes Camuzat, Cecile Jeannequin, Catherine Dode, Junko Takahashi, Robert Bellance, Alexis BriceAbstract:Summary We report a group of 252 patients with a Huntington’s disease-like (HDL) phenotype, including 60 with typical Huntington’s disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington’s disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/ CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington’s disease. Taking into account patients with typical Huntington’s disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
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A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease–like 2
Nature Genetics, 2001Co-Authors: Susan E. Holmes, Giovanni Stevanin, Alexis Brice, Elizabeth O'hearn, Adam Rosenblatt, Colleen Callahan, Hyon S. Hwang, Roxann G. Ingersoll-ashworth, Adam Fleisher, Nicholas T. PotterAbstract:We recently described a disorder termed Huntington disease–like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W)^ 1 . We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
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A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.
Nature Genetics, 2001Co-Authors: Susan E. Holmes, Giovanni Stevanin, Alexis Brice, Elizabeth O'hearn, Adam Rosenblatt, Colleen Callahan, Hyon S. Hwang, Roxann G. Ingersoll-ashworth, Adam Fleisher, Nicholas T. PotterAbstract:We recently described a disorder termed Huntington disease–like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W)1. We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
Fahmida Essop - One of the best experts on this subject based on the ideXlab platform.
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junctophilin 3 JPH3 expansion mutations causing huntington disease like 2 hdl2 are common in south african patients with african ancestry and a huntington disease phenotype
American Journal of Medical Genetics, 2015Co-Authors: Amanda Krause, Christopher A. Ross, Claire Mitchell, Fahmida Essop, Susan Tager, James Temlett, Giovanni Stevanin, Dobrila D. RudnickiAbstract:Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. © 2015 Wiley Periodicals, Inc.
James Temlett - One of the best experts on this subject based on the ideXlab platform.
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junctophilin 3 JPH3 expansion mutations causing huntington disease like 2 hdl2 are common in south african patients with african ancestry and a huntington disease phenotype
American Journal of Medical Genetics, 2015Co-Authors: Amanda Krause, Christopher A. Ross, Claire Mitchell, Fahmida Essop, Susan Tager, James Temlett, Giovanni Stevanin, Dobrila D. RudnickiAbstract:Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disorder, characterized by abnormal movements, cognitive decline, and psychiatric symptoms, caused by a CAG repeat expansion in the huntingtin (HTT) gene on chromosome 4p. A CAG/CTG repeat expansion in the junctophilin-3 (JPH3) gene on chromosome 16q24.2 causes a Huntington disease-like phenotype (HDL2). All patients to date with HDL2 have some African ancestry. The present study aimed to characterize the genetic basis of the Huntington disease phenotype in South Africans and to investigate the possible origin of the JPH3 mutation. In a sample of unrelated South African individuals referred for diagnostic HD testing, 62% (106/171) of white patients compared to only 36% (47/130) of black patients had an expansion in HTT. However, 15% (20/130) of black South African patients and no white patients (0/171) had an expansion in JPH3, confirming the diagnosis of Huntington disease like 2 (HDL2). Individuals with HDL2 share many clinical features with individuals with HD and are clinically indistinguishable in many cases, although the average age of onset and diagnosis in HDL2 is 5 years later than HD and individual clinical features may be more prominent. HDL2 mutations contribute significantly to the HD phenotype in South Africans with African ancestry. JPH3 haplotype studies in 31 families, mainly from South Africa and North America, provide evidence for a founder mutation and support a common African origin for all HDL2 patients. Molecular testing in individuals with an HD phenotype and African ancestry should include testing routinely for JPH3 mutations. © 2015 Wiley Periodicals, Inc.
