Szakszon, Katalin; Lourenco, Charles Marques; Callewaert, Bert Louis; Geneviève, David; Rouxel, Flavien; Morin, Denis; Denommé-Pichon, Anne-Sophie; Vitobello, Antonio; Patterson, Wesley; Louie, Raymond; Pinto E Vairo, Filippo; Klee, Eric; Kaiwar, Charu; Gavrilova, Ralitza H; Agre, Katherine E; Jacquemont, Sebastien; Khadijé, Jizi; Giltay, Jacques; van Gassen, Koen; Merő, Gabriella; ... (2024). Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with ZNF148 mutations. Journal of medical genetics, 61(2), pp. 132-141. BMJ Publishing Group 10.1136/jmg-2022-109030
Full text not available from this repository. (Request a copy)BACKGROUND
Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far.
METHODS
As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals.
RESULTS
The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families.
CONCLUSION
The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term 'GDACCF syndrome' with 'ZNF148-related neurodevelopmental disorder'.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Human Genetics |
UniBE Contributor: |
Fasel, Pascale Denise, Braun, Dominique |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0022-2593 |
Publisher: |
BMJ Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
16 Aug 2023 09:09 |
Last Modified: |
21 Jan 2024 00:12 |
Publisher DOI: |
10.1136/jmg-2022-109030 |
PubMed ID: |
37580113 |
Uncontrolled Keywords: |
Behaviour and Behaviour Mechanisms Epilepsy Genetic Counselling Paediatrics Psychiatry |
URI: |
https://boris.unibe.ch/id/eprint/185471 |
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