A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/36576 http://dx.doi.org/10.5665/sleep.2898 |
Resumo: | Study Objectives: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges.Design: Clinical and genetic investigation in a patient and family members.Setting: Ataxia clinic, São Paulo, Brazil.Patients or Participants: One patient and her family members. Interventions: N/A.Measurements and Results: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06: 02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. the patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. the proband had a novel DNMT1 mutation in exon 21, p. Cys596Arg, c. 1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient.Conclusions: the Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. the mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis. |
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Pedroso, Jose Luiz [UNIFESP]Barsottini, Orlando Graziani Povoas [UNIFESP]Lin, LingMelberg, AtleOliveira, Acary Souza Bulle [UNIFESP]Mignot, EmmanuelUniversidade Federal de São Paulo (UNIFESP)Stanford UnivUppsala Univ2016-01-24T14:32:02Z2016-01-24T14:32:02Z2013-08-01Sleep. Westchester: Amer Acad Sleep Medicine, v. 36, n. 8, p. 1257-1259, 2013.0161-8105http://repositorio.unifesp.br/handle/11600/36576http://dx.doi.org/10.5665/sleep.289810.5665/sleep.2898WOS:000322578500020Study Objectives: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges.Design: Clinical and genetic investigation in a patient and family members.Setting: Ataxia clinic, São Paulo, Brazil.Patients or Participants: One patient and her family members. Interventions: N/A.Measurements and Results: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06: 02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. the patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. the proband had a novel DNMT1 mutation in exon 21, p. Cys596Arg, c. 1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient.Conclusions: the Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. the mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis.Universidade Federal de São Paulo, Dept Neurol, Ataxia Unit, São Paulo, BrazilStanford Univ, Sch Med, Ctr Sleep Sci & Med, Palo Alto, CA 94304 USAStanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USAUppsala Univ, Dept Neurosci, Uppsala, SwedenUniversidade Federal de São Paulo, Dept Neurol, Ataxia Unit, São Paulo, BrazilWeb of Science1257-1259engAmer Acad Sleep MedicineSleepNarcolepsycerebellar ataxiadeafnessnovel DNMT1 mutationde novoA Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patientinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/365762022-09-27 09:38:17.416metadata only accessoai:repositorio.unifesp.br:11600/36576Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T12:38:17Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
title |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
spellingShingle |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient Pedroso, Jose Luiz [UNIFESP] Narcolepsy cerebellar ataxia deafness novel DNMT1 mutation de novo |
title_short |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
title_full |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
title_fullStr |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
title_full_unstemmed |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
title_sort |
A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient |
author |
Pedroso, Jose Luiz [UNIFESP] |
author_facet |
Pedroso, Jose Luiz [UNIFESP] Barsottini, Orlando Graziani Povoas [UNIFESP] Lin, Ling Melberg, Atle Oliveira, Acary Souza Bulle [UNIFESP] Mignot, Emmanuel |
author_role |
author |
author2 |
Barsottini, Orlando Graziani Povoas [UNIFESP] Lin, Ling Melberg, Atle Oliveira, Acary Souza Bulle [UNIFESP] Mignot, Emmanuel |
author2_role |
author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Stanford Univ Uppsala Univ |
dc.contributor.author.fl_str_mv |
Pedroso, Jose Luiz [UNIFESP] Barsottini, Orlando Graziani Povoas [UNIFESP] Lin, Ling Melberg, Atle Oliveira, Acary Souza Bulle [UNIFESP] Mignot, Emmanuel |
dc.subject.eng.fl_str_mv |
Narcolepsy cerebellar ataxia deafness novel DNMT1 mutation de novo |
topic |
Narcolepsy cerebellar ataxia deafness novel DNMT1 mutation de novo |
description |
Study Objectives: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges.Design: Clinical and genetic investigation in a patient and family members.Setting: Ataxia clinic, São Paulo, Brazil.Patients or Participants: One patient and her family members. Interventions: N/A.Measurements and Results: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06: 02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. the patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. the proband had a novel DNMT1 mutation in exon 21, p. Cys596Arg, c. 1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient.Conclusions: the Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. the mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-08-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:32:02Z |
dc.date.available.fl_str_mv |
2016-01-24T14:32:02Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Sleep. Westchester: Amer Acad Sleep Medicine, v. 36, n. 8, p. 1257-1259, 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/36576 http://dx.doi.org/10.5665/sleep.2898 |
dc.identifier.issn.none.fl_str_mv |
0161-8105 |
dc.identifier.doi.none.fl_str_mv |
10.5665/sleep.2898 |
dc.identifier.wos.none.fl_str_mv |
WOS:000322578500020 |
identifier_str_mv |
Sleep. Westchester: Amer Acad Sleep Medicine, v. 36, n. 8, p. 1257-1259, 2013. 0161-8105 10.5665/sleep.2898 WOS:000322578500020 |
url |
http://repositorio.unifesp.br/handle/11600/36576 http://dx.doi.org/10.5665/sleep.2898 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Sleep |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1257-1259 |
dc.publisher.none.fl_str_mv |
Amer Acad Sleep Medicine |
publisher.none.fl_str_mv |
Amer Acad Sleep Medicine |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
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1802764161350893568 |