Genetic and phenotypic spectrum in the NONO-associated syndromic disorder.
RNA expression analysis
X-linked inheritance
corpus callosum anomalies
in-frame splice deletion
neurodevelopmental delay
non-compaction cardiomyopathy
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:
02 2023
02 2023
Historique:
revised:
23
09
2022
received:
23
05
2022
accepted:
30
09
2022
pubmed:
26
11
2022
medline:
13
1
2023
entrez:
25
11
2022
Statut:
ppublish
Résumé
The non-POU domain-containing octamer-binding (NONO) protein is involved in multiple steps of gene regulation such as RNA metabolism and DNA repair. Hemizygous pathogenic variants in the NONO gene were confirmed to cause a rare X-linked syndromic disorder. Through our in-house diagnostics and subsequent matchmaking, we identified six unrelated male individuals with pathogenic or likely pathogenic NONO variants. For a detailed comparison, we reviewed all published characterizations of the NONO-associated disorder. The combined cohort consists of 16 live-born males showing developmental delay, corpus callosum anomalies, non-compaction cardiomyopathy and relative macrocephaly as leading symptoms. Seven prenatal literature cases were characterized by cardiac malformations. In this study, we extend the phenotypic spectrum through two more cases with epilepsy as well as two more cases with hematologic anomalies. By RNA expression analysis and structural modeling of a new in-frame splice deletion, we reinforce loss-of-function as the pathomechanism for the NONO-associated syndromic disorder.
Identifiants
pubmed: 36426740
doi: 10.1002/ajmg.a.63044
doi:
Substances chimiques
DNA-Binding Proteins
0
RNA
63231-63-0
NONO protein, human
0
RNA-Binding Proteins
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
469-478Informations de copyright
© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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