Further delineation of the phenotypic spectrum associated with hemizygous loss-of-function variants in NONO.
NONO
X-linked
X-linked congenital heart defects
genetic syndrome
left ventricular noncompaction
mental retardation, syndromic 34
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
16
09
2019
revised:
23
11
2019
accepted:
12
12
2019
pubmed:
29
12
2019
medline:
4
2
2021
entrez:
29
12
2019
Statut:
ppublish
Résumé
The non-POU domain containing, octamer-binding gene, NONO, is located on chromosome Xq13.1 and encodes a member of a small family of RNA and DNA binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Hemizygous loss-of-function variants in NONO have been shown to cause mental retardation, X-linked, syndromic 34 in males. Features of this disorder can include a range of neurodevelopmental phenotypes, left ventricular noncompaction (LVNC), congenital heart defects, and CNS anomalies. To date only eight cases have been described in the literature. Here we report two unrelated patients and a miscarried fetus with loss-of-function variants in NONO. Their phenotypes, and a review of previously reported cases, demonstrate that hemizygous loss-of-function variants in NONO cause a recognizable genetic syndrome. The cardinal features of this condition include developmental delay, intellectual disability, hypotonia, macrocephaly, structural abnormalities affecting the corpus callosum and/or cerebellum, LVNC, congenital heart defects, and gastrointestinal/feeding issues. This syndrome also carries an increased risk for strabismus and cryptorchidism and is associated with dysmorphic features that include an elongated face, up/down-slanted palpebral fissures, frontal bossing, and malar hypoplasia.
Identifiants
pubmed: 31883306
doi: 10.1002/ajmg.a.61466
doi:
Substances chimiques
DNA-Binding Proteins
0
NONO protein, human
0
RNA-Binding Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
652-658Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
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