Novel heterozygous variants in KMT2D associated with holoprosencephaly.
KMT2D
HPE
holoprosencephaly
human forebrain development
whole exome sequencing
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
29
03
2019
revised:
14
06
2019
accepted:
03
07
2019
pubmed:
10
7
2019
medline:
18
8
2020
entrez:
9
7
2019
Statut:
ppublish
Résumé
Lysine methyltransferase 2D (KMT2D; OMIM 602113) encodes a histone methyltransferase involved in transcriptional regulation of the beta-globin and estrogen receptor as part of a large protein complex known as activating signal cointegrator-2-containing complex (ASCOM). Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder. Neither holoprosencephaly nor other defects in human forebrain development have been previously associated with Kabuki syndrome. Here we report two patients diagnosed with alobar holoprosencephaly in their antenatal period with de novo monoallelic KMT2D variants identified by trio-based exome sequencing. The first patient was found to have a stop-gain variant c.12565G>T (p.Gly4189*), while the second patient had a missense variant c.5A>G (p.Asp2Gly). Phenotyping of each patient did not reveal any age-related feature of Kabuki syndrome. These two cases represent the first report on association between KMT2D and holoprosencephaly.
Identifiants
pubmed: 31282990
doi: 10.1111/cge.13598
pmc: PMC6690755
mid: NIHMS1040456
doi:
Substances chimiques
DNA-Binding Proteins
0
KMT2D protein, human
0
Neoplasm Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
266-270Subventions
Organisme : Intramural NIH HHS
ID : Z99 HG999999
Pays : United States
Informations de copyright
Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
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