Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

Mauricio A. Sáez, Juana Fernández-Rodríguez, Catia Moutinho, Jose V. Sanchez-Mut, Antonio Gomez, Enrique Vidal, Paolo Petazzi, Karolina Szczesna, Paula Lopez-Serra, Mario Lucariello, Patricia Lorden, Raul Delgado-Morales, Olga J. De La Caridad, Dori Huertas, Josep L. Gelpí, Modesto Orozco, Adriana López-Doriga, Montserrat Milà, Luís A. Perez-Jurado, Mercedes PinedaJudith Armstrong, Conxi Lázaro, Manel Esteller

Resultado de la investigación: Article

15 Citas (Scopus)

Resumen

Purpose:Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders.Methods:We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect.Results:We found seven JMJD1C variants that were not present in any control sample (∼ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity.Conclusions:Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.

Idioma originalEnglish
Páginas (desde-hasta)378-385
Número de páginas8
PublicaciónGenetics in Medicine
Volumen18
N.º4
DOI
EstadoPublished - 1 abr 2016

Huella dactilar

Rett Syndrome
Intellectual Disability
Mutation
Jumonji Domain-Containing Histone Demethylases
Histone Demethylases
Viverridae
Proteins
Germ-Line Mutation
DNA Damage
Epilepsy
Communication
Amino Acids
Brain

ASJC Scopus subject areas

  • Genetics(clinical)

Citar esto

Sáez, M. A., Fernández-Rodríguez, J., Moutinho, C., Sanchez-Mut, J. V., Gomez, A., Vidal, E., ... Esteller, M. (2016). Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. Genetics in Medicine, 18(4), 378-385. https://doi.org/10.1038/gim.2015.100
Sáez, Mauricio A. ; Fernández-Rodríguez, Juana ; Moutinho, Catia ; Sanchez-Mut, Jose V. ; Gomez, Antonio ; Vidal, Enrique ; Petazzi, Paolo ; Szczesna, Karolina ; Lopez-Serra, Paula ; Lucariello, Mario ; Lorden, Patricia ; Delgado-Morales, Raul ; De La Caridad, Olga J. ; Huertas, Dori ; Gelpí, Josep L. ; Orozco, Modesto ; López-Doriga, Adriana ; Milà, Montserrat ; Perez-Jurado, Luís A. ; Pineda, Mercedes ; Armstrong, Judith ; Lázaro, Conxi ; Esteller, Manel. / Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. En: Genetics in Medicine. 2016 ; Vol. 18, N.º 4. pp. 378-385.
@article{b1321a25b2ea4c7891af6fc700bcc9cb,
title = "Mutations in JMJD1C are involved in Rett syndrome and intellectual disability",
abstract = "Purpose:Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders.Methods:We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect.Results:We found seven JMJD1C variants that were not present in any control sample (∼ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity.Conclusions:Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.",
keywords = "autism, intellectual disability, mutational screening, Rett syndrome",
author = "S{\'a}ez, {Mauricio A.} and Juana Fern{\'a}ndez-Rodr{\'i}guez and Catia Moutinho and Sanchez-Mut, {Jose V.} and Antonio Gomez and Enrique Vidal and Paolo Petazzi and Karolina Szczesna and Paula Lopez-Serra and Mario Lucariello and Patricia Lorden and Raul Delgado-Morales and {De La Caridad}, {Olga J.} and Dori Huertas and Gelp{\'i}, {Josep L.} and Modesto Orozco and Adriana L{\'o}pez-Doriga and Montserrat Mil{\`a} and Perez-Jurado, {Lu{\'i}s A.} and Mercedes Pineda and Judith Armstrong and Conxi L{\'a}zaro and Manel Esteller",
year = "2016",
month = "4",
day = "1",
doi = "10.1038/gim.2015.100",
language = "English",
volume = "18",
pages = "378--385",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

Sáez, MA, Fernández-Rodríguez, J, Moutinho, C, Sanchez-Mut, JV, Gomez, A, Vidal, E, Petazzi, P, Szczesna, K, Lopez-Serra, P, Lucariello, M, Lorden, P, Delgado-Morales, R, De La Caridad, OJ, Huertas, D, Gelpí, JL, Orozco, M, López-Doriga, A, Milà, M, Perez-Jurado, LA, Pineda, M, Armstrong, J, Lázaro, C & Esteller, M 2016, 'Mutations in JMJD1C are involved in Rett syndrome and intellectual disability', Genetics in Medicine, vol. 18, n.º 4, pp. 378-385. https://doi.org/10.1038/gim.2015.100

Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. / Sáez, Mauricio A.; Fernández-Rodríguez, Juana; Moutinho, Catia; Sanchez-Mut, Jose V.; Gomez, Antonio; Vidal, Enrique; Petazzi, Paolo; Szczesna, Karolina; Lopez-Serra, Paula; Lucariello, Mario; Lorden, Patricia; Delgado-Morales, Raul; De La Caridad, Olga J.; Huertas, Dori; Gelpí, Josep L.; Orozco, Modesto; López-Doriga, Adriana; Milà, Montserrat; Perez-Jurado, Luís A.; Pineda, Mercedes; Armstrong, Judith; Lázaro, Conxi; Esteller, Manel.

En: Genetics in Medicine, Vol. 18, N.º 4, 01.04.2016, p. 378-385.

Resultado de la investigación: Article

TY - JOUR

T1 - Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

AU - Sáez, Mauricio A.

AU - Fernández-Rodríguez, Juana

AU - Moutinho, Catia

AU - Sanchez-Mut, Jose V.

AU - Gomez, Antonio

AU - Vidal, Enrique

AU - Petazzi, Paolo

AU - Szczesna, Karolina

AU - Lopez-Serra, Paula

AU - Lucariello, Mario

AU - Lorden, Patricia

AU - Delgado-Morales, Raul

AU - De La Caridad, Olga J.

AU - Huertas, Dori

AU - Gelpí, Josep L.

AU - Orozco, Modesto

AU - López-Doriga, Adriana

AU - Milà, Montserrat

AU - Perez-Jurado, Luís A.

AU - Pineda, Mercedes

AU - Armstrong, Judith

AU - Lázaro, Conxi

AU - Esteller, Manel

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Purpose:Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders.Methods:We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect.Results:We found seven JMJD1C variants that were not present in any control sample (∼ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity.Conclusions:Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.

AB - Purpose:Autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders.Methods:We performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect.Results:We found seven JMJD1C variants that were not present in any control sample (∼ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity.Conclusions:Our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.Genet Med 18 1, 378-385.

KW - autism

KW - intellectual disability

KW - mutational screening

KW - Rett syndrome

UR - http://www.scopus.com/inward/record.url?scp=84962553399&partnerID=8YFLogxK

U2 - 10.1038/gim.2015.100

DO - 10.1038/gim.2015.100

M3 - Article

C2 - 26181491

AN - SCOPUS:84962553399

VL - 18

SP - 378

EP - 385

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 4

ER -

Sáez MA, Fernández-Rodríguez J, Moutinho C, Sanchez-Mut JV, Gomez A, Vidal E y otros. Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. Genetics in Medicine. 2016 abr 1;18(4):378-385. https://doi.org/10.1038/gim.2015.100