Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.

Abstract

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.

• Authors: Maria B Christensen, Amanda M Levy, Nazanin A Mohammadi, Marcello Niceta, Rauan Kaiyrzhanov, Maria Lisa Dentici, Chadi Al Alam, Viola Alesi, Valérie Benoit, Kailash P Bhatia, Tatjana Bierhals, Christian M Boßelmann, Julien Buratti, Bert Callewaert, Berten Ceulemans, Perrine Charles, Matthias De Wachter, Mohammadreza Dehghani, Erika D'haenens, Martine Doco-Fenzy, Michaela Geßner, Cyrielle Gobert, Ulviyya Guliyeva, Tobias B Haack, Trine B Hammer, Tilman Heinrich, Maja Hempel, Theresia Herget, Ute Hoffmann, Judit Horvath, Henry Houlden, Boris Keren, Christina Kresge, Candy Kumps, Damien Lederer, Alban Lermine, Francesca Magrinelli, Reza Maroofian, Mohammad Yahya Vahidi Mehrjardi, Mahdiyeh Moudi, Amelie J Müller, Anna J Oostra, Beth A Pletcher, David Ros-Pardo, Shanika Samarasekera, Marco Tartaglia, Kristof Van Schil, Julie Vogt, Evangeline Wassmer, Juliane Winkelmann, Maha S Zaki, Michael Zech, Holger Lerche, Francesca Clementina Radio, Paulino Gomez-Puertas, Rikke S Møller, Zeynep Tümer
• Journal: Clinical genetics (Clin Genet) Vol. 102 Issue 2 Pg. 98-109 (08 2022) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 35616059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.

Chemical References

• Transcription Factors

Topics

• Humans
• Intellectual Disability (diagnosis)
• Movement Disorders (complications)
• Neurodevelopmental Disorders (genetics)
• Phenotype
• Seizures (complications, genetics)
• Transcription Factors (genetics)