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Biallelic null variants in ZNF142 cause global developmental delay with familial epilepsy and dysmorphic features


Biallelic variants in ZNF142 at 2q35, which encodes zinc-finger protein 142, cause neurodevelopmental disorder with seizures or dystonia. We identified compound heterozygous null variants in ZNF142, NM_001105537.4:c.[1252C>T];[1274-2A>G],p.[Arg418*];[Glu426*], in Malaysian siblings suffering from global developmental delay with epilepsy and dysmorphism. cDNA analysis showed the marked reduction of ZNF142 transcript level through nonsense-mediated mRNA decay by these novel biallelic variants. The affected siblings present with global developmental delay and epilepsy in common, which were previously described, as well as dysmorphism, which was not recognized. It is important to collect patients with ZNF142 abnormality to define its phenotypic spectrum.

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Fig. 1: Biallelic ZNF142 variants cause global developmental delay with epilepsy and dysmorphic features in affected siblings.
Fig. 2: Schematic presentation of pathogenic variants.


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We would like to thank the family for participating in this study. We also thank N. Watanabe, T. Miyama, M. Sato, S. Sugimoto, and K. Takabe for their technical assistance. Finally, we are grateful to Edanz Group ( for editing a draft of this paper. This work was supported by AMED under grant numbers JP18ek0109280, JP21ek0109486, JP21ek0109549, JP21cm0106503, and JP21ek0109493; by JSPS KAKENHI under grant numbers JP20K08164, JP20K16932, JP20K17936, JP20K07907, JP21k15097, and JP20K17428; and by the Takeda Science Foundation.

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Correspondence to Naomichi Matsumoto.

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The authors declare no competing interests.

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This study was approved by the Institutional Review Board of Yokohama City University School of Medicine. Written informed consent was obtained from all participants.

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Kameyama, S., Mizuguchi, T., Fukuda, H. et al. Biallelic null variants in ZNF142 cause global developmental delay with familial epilepsy and dysmorphic features. J Hum Genet (2021).

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