PT  - JOURNAL ARTICLE
AU  - Szakszon, Katalin
AU  - Lourenco, Charles Marques
AU  - Callewaert, Bert Louis
AU  - Geneviève, David
AU  - Rouxel, Flavien
AU  - Morin, Denis
AU  - Denommé-Pichon, Anne-Sophie
AU  - Vitobello, Antonio
AU  - Patterson, Wesley G
AU  - Louie, Raymond
AU  - Pinto e Vairo, Filippo
AU  - Klee, Eric
AU  - Kaiwar, Charu
AU  - Gavrilova, Ralitza H
AU  - Agre, Katherine E
AU  - Jacquemont, Sebastien
AU  - Khadijé, Jizi
AU  - Giltay, Jacques
AU  - van Gassen, Koen
AU  - Merő, Gabriella
AU  - Gerkes, Erica
AU  - Van Bon, Bregje W
AU  - Rinne, Tuula
AU  - Pfundt, Rolph
AU  - Brunner, Han G
AU  - Caluseriu, Oana
AU  - Grasshoff, Ute
AU  - Kehrer, Martin
AU  - Haack, Tobias B
AU  - Khelifa, Melik Malek
AU  - Bergmann, Anke Katharina
AU  - Cueto-González, Anna Maria
AU  - Martorell, Ariadna Campos
AU  - Ramachandrappa, Shwetha
AU  - Sawyer, Lindsey B
AU  - Fasel, Pascale
AU  - Braun, Dominique
AU  - Isis, Atallah
AU  - Superti-Furga, Andrea
AU  - McNiven, Vanda
AU  - Chitayat, David
AU  - Ahmed, Syed Anas
AU  - Brennenstuhl, Heiko
AU  - Schwaibolf, Eva MC
AU  - Battisti, Gladys
AU  - Parmentier, Benoit
AU  - Stevens, Servi J C
TI  - Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with <em>ZNF148</em> mutations
AID  - 10.1136/jmg-2022-109030
DP  - 2023 Aug 14
TA  - Journal of Medical Genetics
PG  - jmg-2022-109030
4099  - http://jmg.bmj.com/content/early/2023/08/18/jmg-2022-109030.short
4100  - http://jmg.bmj.com/content/early/2023/08/18/jmg-2022-109030.full
AB  - 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’.Data are available upon reasonable request. Not applicable.