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Review
. 2023 Feb;191(2):469-478.
doi: 10.1002/ajmg.a.63044. Epub 2022 Nov 25.

Genetic and phenotypic spectrum in the NONO-associated syndromic disorder

Franziska Roessler  1 , Anita E Beck  2   3 , Ball Susie  4 , Bartolomaeus Tobias  1 , Amber Begtrup  5 , Saskia Biskup  6 , Oana Caluseriu  7 , Norman Delanty  8   9 , Christine Fröhlich  6 , Marie T Greally  8   10 , Maike Karnstedt  1 , Chiara Klöckner  1 , Joanne Kurtzberg  11 , Susanna Schubert  1 , Martin Schulze  6 , Michael Weidenbach  12 , Dominik S Westphal  13   14 , Maire White  8   10 , Cordula M Wolf  15 , Jacob Zyskind  5 , Bernt Popp  1 , Vincent Strehlow  1
Affiliations
Review

Genetic and phenotypic spectrum in the NONO-associated syndromic disorder

Franziska Roessler et al. Am J Med Genet A. 2023 Feb.

Abstract

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.

Keywords: RNA expression analysis; X-linked inheritance; corpus callosum anomalies; in-frame splice deletion; neurodevelopmental delay; non-compaction cardiomyopathy.

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References

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