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

Daphne Lehalle; Pierre Vabres; Arthur Sorlin; Tatjana Bierhals; Magali Avila; Virginie Carmignac; Martin Chevarin; Erin Torti; Yuichi Abe; Tobias Bartolomaeus; Jill Clayton-Smith; Benjamin Cogne; Ivon Cusco; Laurence Duplomb; Eveline De Bont; Yannis Duffourd; Floor Duijkers; Orly Elpeleg; Aviva Fattal; David Genevieve; Maria J. Guillen Sacoto; Anne Guimier; David J. Harris; Maja Hempel; Bertrand Isidor; Thibaud Jouan; Paul Kuentz; Eriko Koshimizu; Klaske Lichtenbelt; Valerie Loik Ramey; Miriam Maik; Sakoto Miyakate; Yoshiko Murakami; Laurent Pasquier; Helio Pedro; Laurie Simone; Krista Sondergaard-Schatz; Judith St-Onge; Julien Thevenon; Irene Valenzuela; Rami Abou Jamra; Koen van Gassen; Mieke M. van Haelst; Silvana van Koningsbruggen; Edgard Verdura; Christa Whelan Habela; Pia Zacher; Jean-Baptiste Riviere; Christel Thauvin-Robinet; Joerg Betschinger; Laurence Faivre

doi:10.1136/jmedgenet-2019-106508

Retour

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

Article de revue

Avec comité de lecture

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

Daphne Lehalle, Pierre Vabres, Arthur Sorlin, Tatjana Bierhals, Magali Avila, Virginie Carmignac, Martin Chevarin, Erin Torti, Yuichi Abe, Tobias Bartolomaeus, …

Journal of medical genetics, Vol.57(12), pp.808-819

01/12/2020

DOI: https://doi.org/10.1136/jmedgenet-2019-106508

PMID: 32409512

Résumé

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features
Créateurs - sans rôle: Daphne Lehalle - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Pierre Vabres - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Arthur Sorlin - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Tatjana Bierhals - Univ Med Ctr Hamburg ppendorf, Inst Human Genet, Martinistr 52, Hamburg, Germany
Magali Avila - Univ Bourgogne Franche Comte, Fac Med, INSERM, LNC,UMR 1231, Dijon, France
Virginie Carmignac - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Martin Chevarin - Inserm
Erin Torti - GeneDx, Gaithersburg, MD USA
Yuichi Abe - Natl Ctr Child Hlth & Dev, Div Neurol, Tokyo, Japan
Tobias Bartolomaeus - Univ Leipzig, Inst Human Genet, Med Ctr, Leipzig, Germany
Jill Clayton-Smith - Manchester Ctr Genom Med, Genom Med, Manchester, Lancs, England
Benjamin Cogne - CHU Nantes, Serv Genet Med, Nantes, France
Ivon Cusco - Univ Hosp Vall dHebron, Dept Clin & Mol Genet, Barcelona, Spain
Laurence Duplomb - Inserm
Eveline De Bont - Ommelander Hosp Groningen, Dept Pediat Oncol, Groningen, Netherlands
Yannis Duffourd - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Floor Duijkers - University of Amsterdam
Orly Elpeleg - Hadassah Hebrew Univ, Monique & Jacques Roboh Dept Genet Res, Med Ctr, Jerusalem, Israel
Aviva Fattal - Tel Aviv Univ, Pediat Neurol Inst, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, Tel Aviv, Israel
David Genevieve - CHRU Montpellier, Hop Arnaud Villeneuve, Dept Genet Med, Montpellier, France
Maria J. Guillen Sacoto - GeneDx, Gaithersburg, MD USA
Anne Guimier - Necker Enfants Malades Hosp, Dept Genet, Paris, Ile De France, France
David J. Harris - Boston Childrens Hosp, Div Genom & Genet, Boston, MA USA
Maja Hempel - Univ Med Ctr Hamburg ppendorf, Inst Human Genet, Martinistr 52, Hamburg, Germany
Bertrand Isidor - CHU Nantes, Serv Genet Med, Nantes, France
Thibaud Jouan - Univ Bourgogne Franche Comte, Fac Med, INSERM, LNC,UMR 1231, Dijon, France
Paul Kuentz - Univ Bourgogne Franche Comte, Fac Med, INSERM, LNC,UMR 1231, Dijon, France
Eriko Koshimizu - Yokohama City Univ, Dept Human Genet, Sch Med, Grad Sch Med, Yokohama, Kanagawa, Japan
Klaske Lichtenbelt - Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands
Valerie Loik Ramey - Boston Childrens Hosp, Div Genom & Genet, Boston, MA USA
Miriam Maik - Hackensack Meridian Hlth Inc, Edison, NJ USA
Sakoto Miyakate - Yokohama City Univ, Dept Human Genet, Grad Sch Med, Yokohama, Kanagawa, Japan
Yoshiko Murakami - Osaka Univ, Res Inst Microbial Dis, Yabumoto Dept Intractable Dis Res, Suita, Osaka, Japan
Laurent Pasquier - CHU Rennes, Serv Genet Clin, CLAD Ouest, Rennes, France
Helio Pedro - Hackensack Meridian Hlth Inc, Edison, NJ USA
Laurie Simone - Hackensack Meridian Hlth Inc, Edison, NJ USA
Krista Sondergaard-Schatz - Johns Hopkins Univ, Sch Med, Dept Med Genet, Baltimore, MD USA
Judith St-Onge - Inserm
Julien Thevenon - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Irene Valenzuela - Univ Hosp Vall dHebron, Dept Clin & Mol Genet, Barcelona, Spain
Rami Abou Jamra - Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany
Koen van Gassen - Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands
Mieke M. van Haelst - Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands
Silvana van Koningsbruggen - Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
Edgard Verdura - Bellvitge Biomed Res Inst IDIBELL, Neurometabol Dis Lab, Barcelona, Spain
Christa Whelan Habela - Johns Hopkins Med, John M Freeman Pediat Epilepsy Ctr, Dept Neurol, Baltimore, MD USA
Pia Zacher - Saxon Epilepsy Ctr Kleinwachau, Radeberg, Germany
Jean-Baptiste Riviere - Univ Bourgogne Franche Comte, Fac Med, INSERM, LNC,UMR 1231, Dijon, France
Christel Thauvin-Robinet - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Joerg Betschinger - Friedrich Miescher Inst Biomed Res, Basel, Switzerland
Laurence Faivre - CHU Dijon, Federat Hosp Univ Med Translat & Anomalies Dev TR, Dijon, France
Détails de publication: Journal of medical genetics, Vol.57(12), pp.808-819
Éditeur: Bmj Publishing Group
Nombre de pages: 12
Note de subvention: ANR13-PDOC-0029 / Agence Nationale de la Recherche; Agence Nationale de la Recherche (ANR) PERIS SLT002/16/00174 / URDCat programme FJCI-2016-28811 / Ministerio de Economia, Industria y Competividad (Juan de la Cierva programme) Conseil Regional de Bourgogne through the Plan d'actions Regional pour l'innovation European Union through the PO FEDER-FSE Bourgogne 2014/2020 programmes Programme Hospitalier de Recherche Clinique National 2010
Identifiants: 99141088009311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article