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Hum Mutat. 2016 Sep;37(9):847-64. doi: 10.1002/humu.23026. Epub 2016 Jul 7.

Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X-Linked Kabuki Syndrome Subtype 2.

Author information

1
Institute of Human Genetics, University Medical Center Goettingen, Goettingen, Germany.
2
Laboratory of Rare and Autoinflammatory Diseases, CHU Montpellier, Montpellier, France.
3
University of Montpellier, Montpellier, France.
4
INSERM UMR1183, Montpellier, France.
5
Institute of Human Genetics, University of Cologne, Cologne, Germany.
6
Medical Genetics Department, Koç University School of Medicine (KUSOM), Istanbul, Turkey.
7
Pediatric Genetics Unit, Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey.
8
Department of Pediatric Genetics, Marmara University Medical Faculty, Istanbul, Turkey.
9
Institute of Human Genetics, University of Duesseldorf, Duesseldorf, Germany.
10
Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Germany.
11
Zentrum für Humangenetik, Medizinische Universität, Innsbruck, Austria.
12
Institute of Human Genetics, Technische Universität München, Munich, Germany.
13
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
14
Genetic Services of Western Australia, Princess Margaret and King Edward Memorial Hospitals, Perth, Australia.
15
Western Australian Register of Developmental Anomalies, Perth, Australia.
16
Telethon Kids Institute, Perth, Australia.
17
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
18
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
19
Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
20
Department of Genetics, APHP-Robert DEBRE University Hospital, Paris VII University, Denis Diderot Medical School, Paris, France.
21
Department of Genetics, Nantes University Hospital, Nantes, France.
22
Department of Medical Genetics, Bordeaux University, CHU Bordeaux, INSERM U1211, Bordeaux, France.
23
Department of Medical Genetics, Reference Center for Developmental Abnormalities, CHU, Montpellier, France.
24
Institut Imagine, Paris Descartes-Sorbonne Paris Cité University, INSERM U1163, Paris, France.
25
Service de Génétique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris, Paris, France.
26
HCL Genetic Department, INSERM U1028 CNRS UMR 5292, UCBL1, CRNL, GENDEV Team, Lyon, France.
27
Department of Medical Genetics, l'Archet II Hospital, Nice, France.

Abstract

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.

KEYWORDS:

KDM6A; KDM6C; KMT2D; Kabuki syndrome; MLL2; UTY

PMID:
27302555
DOI:
10.1002/humu.23026
[Indexed for MEDLINE]

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