RT Journal Article
SR Electronic
T1 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
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmg-2022-109030
DO 10.1136/jmg-2022-109030
A1 Szakszon, Katalin
A1 Lourenco, Charles Marques
A1 Callewaert, Bert Louis
A1 Geneviève, David
A1 Rouxel, Flavien
A1 Morin, Denis
A1 Denommé-Pichon, Anne-Sophie
A1 Vitobello, Antonio
A1 Patterson, Wesley G
A1 Louie, Raymond
A1 Pinto e Vairo, Filippo
A1 Klee, Eric
A1 Kaiwar, Charu
A1 Gavrilova, Ralitza H
A1 Agre, Katherine E
A1 Jacquemont, Sebastien
A1 Khadijé, Jizi
A1 Giltay, Jacques
A1 van Gassen, Koen
A1 Merő, Gabriella
A1 Gerkes, Erica
A1 Van Bon, Bregje W
A1 Rinne, Tuula
A1 Pfundt, Rolph
A1 Brunner, Han G
A1 Caluseriu, Oana
A1 Grasshoff, Ute
A1 Kehrer, Martin
A1 Haack, Tobias B
A1 Khelifa, Melik Malek
A1 Bergmann, Anke Katharina
A1 Cueto-González, Anna Maria
A1 Martorell, Ariadna Campos
A1 Ramachandrappa, Shwetha
A1 Sawyer, Lindsey B
A1 Fasel, Pascale
A1 Braun, Dominique
A1 Isis, Atallah
A1 Superti-Furga, Andrea
A1 McNiven, Vanda
A1 Chitayat, David
A1 Ahmed, Syed Anas
A1 Brennenstuhl, Heiko
A1 Schwaibolf, Eva MC
A1 Battisti, Gladys
A1 Parmentier, Benoit
A1 Stevens, Servi J C
YR 2023
UL http://jmg.bmj.com/content/early/2023/08/18/jmg-2022-109030.abstract
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.