Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder
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Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder. / Christensen, Maria B; Levy, Amanda M; Mohammadi, Nazanin A; Niceta, Marcello; Kaiyrzhanov, Rauan; Dentici, Maria Lisa; Al Alam, Chadi; Alesi, Viola; Benoit, Valérie; Bhatia, Kailash P; Bierhals, Tatjana; Boßelmann, Christian M; Buratti, Julien; Callewaert, Bert; Ceulemans, Berten; Charles, Perrine; De Wachter, Matthias; Dehghani, Mohammadreza; D'haenens, Erika; Doco-Fenzy, Martine; Geßner, Michaela; Gobert, Cyrielle; Guliyeva, Ulviyya; Haack, Tobias B; Hammer, Trine B; Heinrich, Tilman; Hempel, Maja; Herget, Theresia; Hoffmann, Ute; Horvath, Judit; Houlden, Henry; Keren, Boris; Kresge, Christina; Kumps, Candy; Lederer, Damien; Lermine, Alban; Magrinelli, Francesca; Maroofian, Reza; Vahidi Mehrjardi, Mohammad Yahya; Moudi, Mahdiyeh; Müller, Amelie J; Oostra, Anna J; Pletcher, Beth A; Ros-Pardo, David; Samarasekera, Shanika; Tartaglia, Marco; Van Schil, Kristof; Vogt, Julie; Wassmer, Evangeline; Winkelmann, Juliane; Zaki, Maha S; Zech, Michael; Lerche, Holger; Radio, Francesca Clementina; Gomez-Puertas, Paulino; Møller, Rikke S; Tümer, Zeynep.
In: CLIN GENET, Vol. 102, No. 2, 05.2022, p. 98-109.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - © 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
PY - 2022/5
Y1 - 2022/5
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 - Humans
KW - Intellectual Disability/diagnosis
KW - Movement Disorders/complications
KW - Neurodevelopmental Disorders/genetics
KW - Phenotype
KW - Seizures/complications
KW - Transcription Factors/genetics
U2 - 10.1111/cge.14165
DO - 10.1111/cge.14165
M3 - SCORING: Journal article
C2 - 35616059
VL - 102
SP - 98
EP - 109
JO - CLIN GENET
JF - CLIN GENET
SN - 0009-9163
IS - 2
ER -
