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Exonic trinucleotid...
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4 : A poly-glycine disease.
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- Wallenius, Joel (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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- Kafantari, Efthymia (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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- Jhaveri, Emma (författare)
- Skåne University Hospital
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visa fler...
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- Gorcenco, Sorina (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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- Ameur, Adam (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Karremo, Christin (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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- Dobloug, Sigurd (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Helsingborg Hospital,Skåne University Hospital
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- Karrman, Kristina (författare)
- Lund University,Lunds universitet,Genetiska och epigenetiska studier av barnleukemi,Forskargrupper vid Lunds universitet,Genetic and epigenetic studies of pediatric leukemia,Lund University Research Groups,Region Skåne
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- de Koning, Tom (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Ilinca, Andreea (författare)
- Lund University,Lunds universitet,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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- Landqvist Waldö, Maria (författare)
- Lund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Arvidsson, Andreas (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Persson, Staffan (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Englund, Elisabet (författare)
- Lund University,Lunds universitet,Skåne University Hospital,Region Skåne
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- Ehrencrona, Hans (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Region Skåne
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- Puschmann, Andreas (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk neurogenetik,Forskargrupper vid Lunds universitet,SciLifeLab Site@Lund,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Neurogenetics,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 111:1, s. 82-95
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Autosomal-dominant ataxia with sensory and autonomic neuropathy is a highly specific combined phenotype that we described in two Swedish kindreds in 2014; its genetic cause had remained unknown. Here, we report the discovery of exonic GGC trinucleotide repeat expansions, encoding poly-glycine, in zinc finger homeobox 3 (ZFHX3) in these families. The expansions were identified in whole-genome datasets within genomic segments that all affected family members shared. Non-expanded alleles carried one or more interruptions within the repeat. We also found ZFHX3 repeat expansions in three additional families, all from the region of Skåne in southern Sweden. Individuals with expanded repeats developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. Anticipation was observed in all families and correlated with different repeat lengths determined through long-read sequencing in two family members. The most severely affected individuals had marked autonomic dysfunction, with severe orthostatism as the most disabling clinical feature. Neuropathology revealed p62-positive intracytoplasmic and intranuclear inclusions in neurons of the central and enteric nervous system, as well as alpha-synuclein positivity. ZFHX3 is located within the 16q22 locus, to which spinocerebellar ataxia type 4 (SCA4) repeatedly had been mapped; the clinical phenotype in our families corresponded well with the unique phenotype described in SCA4, and the original SCA4 kindred originated from Sweden. ZFHX3 has known functions in neuronal development and differentiation n both the central and peripheral nervous system. Our findings demonstrate that SCA4 is caused by repeat expansions in ZFHX3.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- GGC repeats
- SCA4
- ZFHX3
- anticipation
- autosomal dominant
- interruptions
- p62-positive inclusions
- poly-glycine
- spinocerebellar ataxia 4
- trinucelotide repeats
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Wallenius, Joel
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Kafantari, Efthy ...
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Jhaveri, Emma
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Gorcenco, Sorina
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Ameur, Adam
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Karremo, Christi ...
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visa fler...
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Dobloug, Sigurd
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Karrman, Kristin ...
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de Koning, Tom
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Ilinca, Andreea
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Landqvist Waldö, ...
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Arvidsson, Andre ...
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Persson, Staffan
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Englund, Elisabe ...
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Ehrencrona, Hans
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Puschmann, Andre ...
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- Av lärosätet
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Uppsala universitet
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