TY - JOUR

T1 - Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder

AU - Christensen, Maria B.

AU - Levy, Amanda M.

AU - Mohammadi, Nazanin A.

AU - Niceta, Marcello

AU - Kaiyrzhanov, Rauan

AU - Dentici, Maria Lisa

AU - Al Alam, Chadi

AU - Alesi, Viola

AU - Benoit, Valérie

AU - Bhatia, Kailash P.

AU - Bierhals, Tatjana

AU - Boßelmann, Christian M.

AU - Buratti, Julien

AU - Callewaert, Bert

AU - Ceulemans, Berten

AU - Charles, Perrine

AU - De Wachter, Matthias

AU - Dehghani, Mohammadreza

AU - D'haenens, Erika

AU - Doco-Fenzy, Martine

AU - Geßner, Michaela

AU - Gobert, Cyrielle

AU - Guliyeva, Ulviyya

AU - Haack, Tobias B.

AU - Hammer, Trine B.

AU - Heinrich, Tilman

AU - Hempel, Maja

AU - Herget, Theresia

AU - Hoffmann, Ute

AU - Horvath, Judit

AU - Houlden, Henry

AU - Keren, Boris

AU - Kresge, Christina

AU - Kumps, Candy

AU - Lederer, Damien

AU - Lermine, Alban

AU - Magrinelli, Francesca

AU - Maroofian, Reza

AU - Vahidi Mehrjardi, Mohammad Yahya

AU - Moudi, Mahdiyeh

AU - Müller, Amelie J.

AU - Oostra, Anna J.

AU - Pletcher, Beth A.

AU - Ros-Pardo, David

AU - Samarasekera, Shanika

AU - Tartaglia, Marco

AU - Van Schil, Kristof

AU - Vogt, Julie

AU - Wassmer, Evangeline

AU - Winkelmann, Juliane

AU - Zaki, Maha S.

AU - Zech, Michael

AU - Lerche, Holger

AU - Radio, Francesca Clementina

AU - Gomez-Puertas, Paulino

AU - Møller, Rikke S.

AU - Tümer, Zeynep

N1 - Publisher Copyright: © 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - epilepsy

KW - intellectual disability

KW - language impairement

KW - movement disorder

KW - neurodevelopmental disorder

KW - ZNF142

U2 - 10.1111/cge.14165

DO - 10.1111/cge.14165

M3 - Journal article

C2 - 35616059

AN - SCOPUS:85131360858

VL - 102

SP - 98

EP - 109

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 2

ER -