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Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families

BackgroundEpilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR.Methods and resultsHere, we a... Full description

Journal Title: Journal of Medical Genetics 2010, Vol.47 (3), p.211-216
Main Author: Hynes, Kim
Other Authors: Tarpey, Patrick , Dibbens, Leanne M , Bayly, Marta A , Berkovic, Samuel F , Smith, Raffaella , Raisi, Zahyia Al , Turner, Samantha J , Brown, Natasha J , Desai, Tarishi D , Haan, Eric , Turner, Gillian , Christodoulou, John , Leonard, Helen , Gill, Deepak , Stratton, Michael R , Gecz, Jozef , Scheffer, Ingrid E
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: London: BMJ Publishing Group Ltd
ID: ISSN: 0022-2593
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title: Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families
format: Article
creator:
  • Hynes, Kim
  • Tarpey, Patrick
  • Dibbens, Leanne M
  • Bayly, Marta A
  • Berkovic, Samuel F
  • Smith, Raffaella
  • Raisi, Zahyia Al
  • Turner, Samantha J
  • Brown, Natasha J
  • Desai, Tarishi D
  • Haan, Eric
  • Turner, Gillian
  • Christodoulou, John
  • Leonard, Helen
  • Gill, Deepak
  • Stratton, Michael R
  • Gecz, Jozef
  • Scheffer, Ingrid E
subjects:
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Biological and medical sciences
  • Cadherins
  • Cadherins - genetics
  • Child
  • Child Development Disorders, Pervasive - genetics
  • Development and progression
  • EFMR
  • Epilepsy
  • Epilepsy - complications
  • Epilepsy - genetics
  • epilepsy and seizures
  • Family
  • Family Characteristics
  • Female
  • Fundamental and applied biological sciences. Psychology
  • Gene mutations
  • General aspects. Genetic counseling
  • Genetic aspects
  • genetics
  • Genetics of eukaryotes. Biological and molecular evolution
  • Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
  • Humans
  • intellectual disability
  • Medical genetics
  • Medical sciences
  • Mental retardation
  • Mental Retardation, X-Linked - complications
  • Mental Retardation, X-Linked - genetics
  • Molecular and cellular biology
  • Molecular Sequence Data
  • Mutation - physiology
  • Nervous system (semeiology, syndromes)
  • Neurology
  • PCDH19
  • Pedigree
  • seizures
  • Sequence Homology, Amino Acid
ispartof: Journal of Medical Genetics, 2010, Vol.47 (3), p.211-216
description: BackgroundEpilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR.Methods and resultsHere, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C→G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19.ConclusionsThis de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0022-2593
fulltext: fulltext
issn:
  • 0022-2593
  • 1468-6244
url: Link


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titleEpilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families
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creatorHynes, Kim ; Tarpey, Patrick ; Dibbens, Leanne M ; Bayly, Marta A ; Berkovic, Samuel F ; Smith, Raffaella ; Raisi, Zahyia Al ; Turner, Samantha J ; Brown, Natasha J ; Desai, Tarishi D ; Haan, Eric ; Turner, Gillian ; Christodoulou, John ; Leonard, Helen ; Gill, Deepak ; Stratton, Michael R ; Gecz, Jozef ; Scheffer, Ingrid E
creatorcontribHynes, Kim ; Tarpey, Patrick ; Dibbens, Leanne M ; Bayly, Marta A ; Berkovic, Samuel F ; Smith, Raffaella ; Raisi, Zahyia Al ; Turner, Samantha J ; Brown, Natasha J ; Desai, Tarishi D ; Haan, Eric ; Turner, Gillian ; Christodoulou, John ; Leonard, Helen ; Gill, Deepak ; Stratton, Michael R ; Gecz, Jozef ; Scheffer, Ingrid E
descriptionBackgroundEpilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR.Methods and resultsHere, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C→G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19.ConclusionsThis de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.
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subjectAdult ; Amino Acid Sequence ; Base Sequence ; Biological and medical sciences ; Cadherins ; Cadherins - genetics ; Child ; Child Development Disorders, Pervasive - genetics ; Development and progression ; EFMR ; Epilepsy ; Epilepsy - complications ; Epilepsy - genetics ; epilepsy and seizures ; Family ; Family Characteristics ; Female ; Fundamental and applied biological sciences. Psychology ; Gene mutations ; General aspects. Genetic counseling ; Genetic aspects ; genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; intellectual disability ; Medical genetics ; Medical sciences ; Mental retardation ; Mental Retardation, X-Linked - complications ; Mental Retardation, X-Linked - genetics ; Molecular and cellular biology ; Molecular Sequence Data ; Mutation - physiology ; Nervous system (semeiology, syndromes) ; Neurology ; PCDH19 ; Pedigree ; seizures ; Sequence Homology, Amino Acid
ispartofJournal of Medical Genetics, 2010, Vol.47 (3), p.211-216
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3Bayly, Marta A
4Berkovic, Samuel F
5Smith, Raffaella
6Raisi, Zahyia Al
7Turner, Samantha J
8Brown, Natasha J
9Desai, Tarishi D
10Haan, Eric
11Turner, Gillian
12Christodoulou, John
13Leonard, Helen
14Gill, Deepak
15Stratton, Michael R
16Gecz, Jozef
17Scheffer, Ingrid E
title
0Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families
1Journal of Medical Genetics
addtitleJ Med Genet
descriptionBackgroundEpilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR.Methods and resultsHere, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C→G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19.ConclusionsThis de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.
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26Medical genetics
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32Molecular Sequence Data
33Mutation - physiology
34Nervous system (semeiology, syndromes)
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39Sequence Homology, Amino Acid
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titleEpilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families
authorHynes, Kim ; Tarpey, Patrick ; Dibbens, Leanne M ; Bayly, Marta A ; Berkovic, Samuel F ; Smith, Raffaella ; Raisi, Zahyia Al ; Turner, Samantha J ; Brown, Natasha J ; Desai, Tarishi D ; Haan, Eric ; Turner, Gillian ; Christodoulou, John ; Leonard, Helen ; Gill, Deepak ; Stratton, Michael R ; Gecz, Jozef ; Scheffer, Ingrid E
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8Development and progression
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14Family
15Family Characteristics
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17Fundamental and applied biological sciences. Psychology
18Gene mutations
19General aspects. Genetic counseling
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31Molecular and cellular biology
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abstractBackgroundEpilepsy and mental retardation limited to females (EFMR) is an intriguing X-linked disorder affecting heterozygous females and sparing hemizygous males. Mutations in the protocadherin 19 (PCDH19) gene have been identified in seven unrelated families with EFMR.Methods and resultsHere, we assessed the frequency of PCDH19 mutations in individuals with clinical features which overlap those of EFMR. We analysed 185 females from three cohorts: 42 with Rett syndrome who were negative for MECP2 and CDKL5 mutations, 57 with autism spectrum disorders, and 86 with epilepsy with or without intellectual disability. No mutations were identified in the Rett syndrome and autism spectrum disorders cohorts suggesting that despite sharing similar clinical characteristics with EFMR, PCDH19 mutations are not generally associated with these disorders. Among the 86 females with epilepsy (of whom 51 had seizure onset before 3 years), with or without intellectual disability, we identified two (2.3%) missense changes. One (c.1671C→G, p.N557K), reported previously without clinical data, was found in two affected sisters, the first EFMR family without a multigenerational family history of affected females. The second, reported here, is a novel de novo missense change identified in a sporadic female. The change, p.S276P, is predicted to result in functional disturbance of PCDH19 as it affects a highly conserved residue adjacent to the adhesion interface of EC3 of PCDH19.ConclusionsThis de novo PCDH19 mutation in a sporadic female highlights that mutational analysis should be considered in isolated instances of girls with infantile onset seizures and developmental delay, in addition to those with the characteristic family history of EFMR.
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