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De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features

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De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features. / Lehalle, Daphné; Vabres, Pierre; Sorlin, Arthur; Bierhals, Tatjana; Avila, Magali; Carmignac, Virginie; Chevarin, Martin; Torti, Erin; Abe, Yuichi; Bartolomaeus, Tobias; Clayton-Smith, Jill; Cogné, Benjamin; Cusco, Ivon; Duplomb, Laurence; De Bont, Eveline; Duffourd, Yannis; Duijkers, Floor; Elpeleg, Orly; Fattal, Aviva; Geneviève, David; Guillen Sacoto, Maria J; Guimier, Anne; Harris, David J; Hempel, Maja; Isidor, Bertrand; Jouan, Thibaud; Kuentz, Paul; Koshimizu, Eriko; Lichtenbelt, Klaske; Loik Ramey, Valerie; Maik, Miriam; Miyakate, Sakoto; Murakami, Yoshiko; Pasquier, Laurent; Pedro, Helio; Simone, Laurie; Sondergaard-Schatz, Krista; St-Onge, Judith; Thevenon, Julien; Valenzuela, Irene; Abou Jamra, Rami; van Gassen, Koen; van Haelst, Mieke M; van Koningsbruggen, Silvana; Verdura, Edgard; Whelan Habela, Christa; Zacher, Pia; Rivière, Jean-Baptiste; Thauvin-Robinet, Christel; Betschinger, Joerg; Faivre, Laurence.

in: J MED GENET, Jahrgang 57, Nr. 12, 12.2020, S. 808-819.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lehalle, D, Vabres, P, Sorlin, A, Bierhals, T, Avila, M, Carmignac, V, Chevarin, M, Torti, E, Abe, Y, Bartolomaeus, T, Clayton-Smith, J, Cogné, B, Cusco, I, Duplomb, L, De Bont, E, Duffourd, Y, Duijkers, F, Elpeleg, O, Fattal, A, Geneviève, D, Guillen Sacoto, MJ, Guimier, A, Harris, DJ, Hempel, M, Isidor, B, Jouan, T, Kuentz, P, Koshimizu, E, Lichtenbelt, K, Loik Ramey, V, Maik, M, Miyakate, S, Murakami, Y, Pasquier, L, Pedro, H, Simone, L, Sondergaard-Schatz, K, St-Onge, J, Thevenon, J, Valenzuela, I, Abou Jamra, R, van Gassen, K, van Haelst, MM, van Koningsbruggen, S, Verdura, E, Whelan Habela, C, Zacher, P, Rivière, J-B, Thauvin-Robinet, C, Betschinger, J & Faivre, L 2020, 'De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features', J MED GENET, Jg. 57, Nr. 12, S. 808-819. https://doi.org/10.1136/jmedgenet-2019-106508

APA

Lehalle, D., Vabres, P., Sorlin, A., Bierhals, T., Avila, M., Carmignac, V., Chevarin, M., Torti, E., Abe, Y., Bartolomaeus, T., Clayton-Smith, J., Cogné, B., Cusco, I., Duplomb, L., De Bont, E., Duffourd, Y., Duijkers, F., Elpeleg, O., Fattal, A., ... Faivre, L. (2020). De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features. J MED GENET, 57(12), 808-819. https://doi.org/10.1136/jmedgenet-2019-106508

Vancouver

Lehalle D, Vabres P, Sorlin A, Bierhals T, Avila M, Carmignac V et al. De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features. J MED GENET. 2020 Dez;57(12):808-819. https://doi.org/10.1136/jmedgenet-2019-106508

Bibtex

@article{3ed1aaee03564e38bae973468d93330f,
title = "De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features",
abstract = "INTRODUCTION: Pigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko's lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.MATERIALS AND METHODS: Subsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or without PM.RESULTS: We describe the detailed clinical and molecular data of 17 individuals harbouring a de novo TFE3 variant, including the patients that initially allowed reporting TFE3 as a new disease-causing gene. The 12 females and 5 males presented with pigmentation anomalies on Blaschko's lines, severe ID, epilepsy, storage disorder-like features, growth retardation and recognisable facial dysmorphism. The variant was at a mosaic state in at least two male patients. All variants were missense except one splice variant. Eleven of the 13 variants were localised in exon 4, 2 in exon 3, and 3 were recurrent variants.CONCLUSION: This series further delineates the specific storage disorder-like phenotype with PM ascribed to de novo TFE3 mutation in exons 3 and 4. It confirms the identification of a novel X-linked human condition associated with mosaicism and dysregulation within the mechanistic target of rapamycin (mTOR) pathway, as well as a link between lysosomal signalling and human development.",
author = "Daphn{\'e} Lehalle and Pierre Vabres and Arthur Sorlin and Tatjana Bierhals and Magali Avila and Virginie Carmignac and Martin Chevarin and Erin Torti and Yuichi Abe and Tobias Bartolomaeus and Jill Clayton-Smith and Benjamin Cogn{\'e} and Ivon Cusco and Laurence Duplomb and {De Bont}, Eveline and Yannis Duffourd and Floor Duijkers and Orly Elpeleg and Aviva Fattal and David Genevi{\`e}ve and {Guillen Sacoto}, {Maria J} and Anne Guimier and Harris, {David J} and Maja Hempel and Bertrand Isidor and Thibaud Jouan and Paul Kuentz and Eriko Koshimizu and Klaske Lichtenbelt and {Loik Ramey}, Valerie and Miriam Maik and Sakoto Miyakate and Yoshiko Murakami and Laurent Pasquier and Helio Pedro and Laurie Simone and Krista Sondergaard-Schatz and Judith St-Onge and Julien Thevenon and Irene Valenzuela and {Abou Jamra}, Rami and {van Gassen}, Koen and {van Haelst}, {Mieke M} and {van Koningsbruggen}, Silvana and Edgard Verdura and {Whelan Habela}, Christa and Pia Zacher and Jean-Baptiste Rivi{\`e}re and Christel Thauvin-Robinet and Joerg Betschinger and Laurence Faivre",
note = "{\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2020",
month = dec,
doi = "10.1136/jmedgenet-2019-106508",
language = "English",
volume = "57",
pages = "808--819",
journal = "J MED GENET",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",
number = "12",

}

RIS

TY - JOUR

T1 - De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features

AU - Lehalle, Daphné

AU - Vabres, Pierre

AU - Sorlin, Arthur

AU - Bierhals, Tatjana

AU - Avila, Magali

AU - Carmignac, Virginie

AU - Chevarin, Martin

AU - Torti, Erin

AU - Abe, Yuichi

AU - Bartolomaeus, Tobias

AU - Clayton-Smith, Jill

AU - Cogné, Benjamin

AU - Cusco, Ivon

AU - Duplomb, Laurence

AU - De Bont, Eveline

AU - Duffourd, Yannis

AU - Duijkers, Floor

AU - Elpeleg, Orly

AU - Fattal, Aviva

AU - Geneviève, David

AU - Guillen Sacoto, Maria J

AU - Guimier, Anne

AU - Harris, David J

AU - Hempel, Maja

AU - Isidor, Bertrand

AU - Jouan, Thibaud

AU - Kuentz, Paul

AU - Koshimizu, Eriko

AU - Lichtenbelt, Klaske

AU - Loik Ramey, Valerie

AU - Maik, Miriam

AU - Miyakate, Sakoto

AU - Murakami, Yoshiko

AU - Pasquier, Laurent

AU - Pedro, Helio

AU - Simone, Laurie

AU - Sondergaard-Schatz, Krista

AU - St-Onge, Judith

AU - Thevenon, Julien

AU - Valenzuela, Irene

AU - Abou Jamra, Rami

AU - van Gassen, Koen

AU - van Haelst, Mieke M

AU - van Koningsbruggen, Silvana

AU - Verdura, Edgard

AU - Whelan Habela, Christa

AU - Zacher, Pia

AU - Rivière, Jean-Baptiste

AU - Thauvin-Robinet, Christel

AU - Betschinger, Joerg

AU - Faivre, Laurence

N1 - © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/12

Y1 - 2020/12

N2 - INTRODUCTION: Pigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko's lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.MATERIALS AND METHODS: Subsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or without PM.RESULTS: We describe the detailed clinical and molecular data of 17 individuals harbouring a de novo TFE3 variant, including the patients that initially allowed reporting TFE3 as a new disease-causing gene. The 12 females and 5 males presented with pigmentation anomalies on Blaschko's lines, severe ID, epilepsy, storage disorder-like features, growth retardation and recognisable facial dysmorphism. The variant was at a mosaic state in at least two male patients. All variants were missense except one splice variant. Eleven of the 13 variants were localised in exon 4, 2 in exon 3, and 3 were recurrent variants.CONCLUSION: This series further delineates the specific storage disorder-like phenotype with PM ascribed to de novo TFE3 mutation in exons 3 and 4. It confirms the identification of a novel X-linked human condition associated with mosaicism and dysregulation within the mechanistic target of rapamycin (mTOR) pathway, as well as a link between lysosomal signalling and human development.

AB - INTRODUCTION: Pigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko's lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.MATERIALS AND METHODS: Subsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or without PM.RESULTS: We describe the detailed clinical and molecular data of 17 individuals harbouring a de novo TFE3 variant, including the patients that initially allowed reporting TFE3 as a new disease-causing gene. The 12 females and 5 males presented with pigmentation anomalies on Blaschko's lines, severe ID, epilepsy, storage disorder-like features, growth retardation and recognisable facial dysmorphism. The variant was at a mosaic state in at least two male patients. All variants were missense except one splice variant. Eleven of the 13 variants were localised in exon 4, 2 in exon 3, and 3 were recurrent variants.CONCLUSION: This series further delineates the specific storage disorder-like phenotype with PM ascribed to de novo TFE3 mutation in exons 3 and 4. It confirms the identification of a novel X-linked human condition associated with mosaicism and dysregulation within the mechanistic target of rapamycin (mTOR) pathway, as well as a link between lysosomal signalling and human development.

U2 - 10.1136/jmedgenet-2019-106508

DO - 10.1136/jmedgenet-2019-106508

M3 - SCORING: Journal article

C2 - 32409512

VL - 57

SP - 808

EP - 819

JO - J MED GENET

JF - J MED GENET

SN - 0022-2593

IS - 12

ER -