Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X-Linked Kabuki Syndrome Subtype 2
Nina Bögershausen
(1)
,
Vincent Gatinois
(2, 3)
,
Vera Riehmer
(4)
,
Hulya Kayserili
(5)
,
Jutta Becker
(4)
,
Michaela Thoenes
(4)
,
Pelin Ozlem Simsek-Kiper
(6)
,
Mouna Barat-Houari
(7)
,
Nursel Elcioglu
(8)
,
Dagmar Wieczorek
(9)
,
Sigrid Tinschert
(10, 11)
,
Guillaume Sarrabay
(3, 2)
,
Tim M. Strom
(12, 13)
,
Aurélie C.S. Fabre
(14, 2)
,
Gareth Baynam
(15)
,
Elodie Sanchez
(2, 3)
,
Gudrun Nürnberg
(16)
,
Umut Altunoglu
(17)
,
Yline Capri
(18)
,
Bertrand Isidor
(19)
,
Didier Lacombe
(20, 21)
,
Carole Corsini
(2, 3)
,
Valerie Cormier-Daire
(22, 23)
,
Damien Sanlaville
(24)
,
Fabienne Giuliano
(25)
,
Kim-Hanh Le Quan Sang
(22)
,
Honorine Kayirangwa
(22)
,
Peter Nurnberg
(16)
,
Thomas Meitinger
(12, 13)
,
Koray Boduroglu
(6)
,
Barbara Zoll
(1)
,
Stanislas Lyonnet
(22, 23)
,
Andreas Tzschach
(10)
,
Alain Verloes
(26)
,
Nataliya Di Donato
(10)
,
Isabelle Touitou
(7, 3, 2)
,
Christian Netzer
(4)
,
Yun Li
(1)
,
David Geneviève
(3, 27)
,
Gökhan Yigit
(1)
,
Bernd Wollnik
(1)
1
UMG -
University Medical Center Göttingen
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
4 University Hospital of Cologne [Cologne]
5 Koç University
6 Faculty of Medicine [Hacettepe University]
7 CHU Montpellier
8 Marmara University [Kadıköy - İstanbul]
9 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
10 TU Dresden - Technische Universität Dresden = Dresden University of Technology
11 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
12 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
13 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
14 UM - Université de Montpellier
15 UWA - The University of Western Australia
16 University of Cologne
17 Departement of Genetics [University of Istanbul]
18 Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré]
19 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
20 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
21 U1211 INSERM/MRGM - Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux)
22 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
23 Hôpital Necker - Enfants Malades [AP-HP]
24 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
25 CHU Nice - Centre Hospitalier Universitaire de Nice
26 Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré]
27 Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier]
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
4 University Hospital of Cologne [Cologne]
5 Koç University
6 Faculty of Medicine [Hacettepe University]
7 CHU Montpellier
8 Marmara University [Kadıköy - İstanbul]
9 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
10 TU Dresden - Technische Universität Dresden = Dresden University of Technology
11 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
12 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
13 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
14 UM - Université de Montpellier
15 UWA - The University of Western Australia
16 University of Cologne
17 Departement of Genetics [University of Istanbul]
18 Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré]
19 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
20 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
21 U1211 INSERM/MRGM - Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux)
22 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
23 Hôpital Necker - Enfants Malades [AP-HP]
24 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
25 CHU Nice - Centre Hospitalier Universitaire de Nice
26 Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré]
27 Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier]
Vincent Gatinois
- Fonction : Auteur
- PersonId : 781146
- ORCID : 0000-0003-0480-6709
Dagmar Wieczorek
- Fonction : Auteur
- PersonId : 894652
Sigrid Tinschert
- Fonction : Auteur
- PersonId : 886288
Guillaume Sarrabay
- Fonction : Auteur
- PersonId : 21364
- IdHAL : guillaume-sarrabay
Valerie Cormier-Daire
- Fonction : Auteur
- PersonId : 902650
Damien Sanlaville
- Fonction : Auteur
- PersonId : 760022
- ORCID : 0000-0001-9939-2849
- IdRef : 059247878
Stanislas Lyonnet
- Fonction : Auteur
- PersonId : 895056
Andreas Tzschach
- Fonction : Auteur
- PersonId : 891891
Alain Verloes
- Fonction : Auteur
- PersonId : 757590
- ORCID : 0000-0003-4819-0264
Résumé
Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype-genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients.