Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 9,14 MB, PDF-dokument
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 The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical Genetics |
| Vol/bind | 102 |
| Udgave nummer | 2 |
| Sider (fra-til) | 98-109 |
| Antal sider | 12 |
| ISSN | 0009-9163 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Several of the authors of this publication are members of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN‐ITHACA [EU Framework Partnership Agreement ID: 3HP‐HP‐FPA ERN‐01‐2016/739516]. Dr. Kamal Kallab is acknowledged for his contribution to this study and Ann Löfgren for her technical assistance. Bert Callewaert is a senior clinical investigator of the Research Foundation – Flanders. Kailash P. Bhatia has received grant support from EU Horizon 2020. Paulino Gomez‐Puertas and David Ros‐Pardo are supported by Spanish government grants RTC‐2017‐6494, RTI2018‐094434‐B‐I00 (MCIU/AEI/FEDER, UE), DTS20‐00024 (ISCIII), the European JPIAMR network “EPIC‐Alliance” and computational support of the “Centro de Computación Científica CCC‐UAM. Tobias Haack was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 418081722, 433158657. Henry Houlden is supported by MRC, Wellcome Trust, Rosetrees Trust, SOLVE‐RD, and the NIHR BRC. Part of Rauan Kiyrzhanov's research is funded in part, by the Wellcome Trust (WT093205MA,
Funding Information:
BMBF (Treat‐ION), Grant/Award Number: 01GM1907A; Deutsche Forschungsgemeinschaft, Grant/Award Number: 418081722 433158657; DFG FOR‐2715, Grant/Award Number: Le1030/16‐2 Le1030/23‐1; Edmond J. Safra Foundation; EU Horizon 2020; Italian Ministry of Health, Grant/Award Numbers: CCR‐2017‐23669081 RCR‐2020‐23670068_001 RCR‐2019‐23669117_001, RF‐2018‐12366931; Medical Research Council, Grant/Award Number: MR/S01165X/1 MR/S005021/1 G0601943; Michael J. Fox Foundation; UCLH Biomedical Research Centre; Rosetrees Trust; SOLVE‐RD; Spanish government grants RTC‐2017‐6494, RTI2018‐094434‐B‐I00 (MCIU/AEI/FEDER, UE), DTS20‐00024 (ISCIII); the European JPIAMR network “EPIC‐Alliance”; Wellcome Trust; Wellcome Trust (WT093205MA, WT104033AIA and the Synaptopathies Strategic Award, 165908) Funding information
Funding Information:
WT104033AIA and the Synaptopathies Strategic Award, 165908), and the Medical Research Council (MR/S01165X/1, MR/S005021/1, G0601943). Holger Lerche is supported by BMBF (Treat‐ION, 01GM1907A), DFG FOR‐2715 (Le1030/16‐2, Le1030/23‐1). Francesca Magrinelli is supported by the Michael J. Fox Foundation (MJFF) and Edmond J. Safra Foundation. Francesca Clementina Radio is supported by Italian Ministry of Health (RF‐2018‐12366931). Marco Tartaglia is supported by Italian Ministry of Health (CCR‐2017‐23669081, RCR‐2020‐23670068_001, RCR‐2019‐23669117_001).
Funding Information:
Several of the authors of this publication are members of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA [EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516]. Dr. Kamal Kallab is acknowledged for his contribution to this study and Ann Löfgren for her technical assistance. Bert Callewaert is a senior clinical investigator of the Research Foundation – Flanders. Kailash P. Bhatia has received grant support from EU Horizon 2020. Paulino Gomez-Puertas and David Ros-Pardo are supported by Spanish government grants RTC-2017-6494, RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE), DTS20-00024 (ISCIII), the European JPIAMR network “EPIC-Alliance” and computational support of the “Centro de Computación Científica CCC-UAM. Tobias Haack was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 418081722, 433158657. Henry Houlden is supported by MRC, Wellcome Trust, Rosetrees Trust, SOLVE-RD, and the NIHR BRC. Part of Rauan Kiyrzhanov's research is funded in part, by the Wellcome Trust (WT093205MA, WT104033AIA and the Synaptopathies Strategic Award, 165908), and the Medical Research Council (MR/S01165X/1, MR/S005021/1, G0601943). Holger Lerche is supported by BMBF (Treat-ION, 01GM1907A), DFG FOR-2715 (Le1030/16-2, Le1030/23-1). Francesca Magrinelli is supported by the Michael J. Fox Foundation (MJFF) and Edmond J. Safra Foundation. Francesca Clementina Radio is supported by Italian Ministry of Health (RF-2018-12366931). Marco Tartaglia is supported by Italian Ministry of Health (CCR-2017-23669081, RCR-2020-23670068_001, RCR-2019-23669117_001).
Publisher Copyright:
© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
ID: 314145840