TCF12 microdeletion in a 72‐year‐old woman with intellectual disability

Abstract

Heterozygous mutations in TCF12 were recently identified as an important cause of craniosynostosis. In the original series, 14% of patients with a mutation in TCF12 had significant developmental delay or learning disability. We report on the first case of TCF12 microdeletion, detected by array‐comparative genomic hybridization, in a 72‐year‐old patient presenting with intellectual deficiency and dysmorphism. Multiplex ligation‐dependent probe amplification analysis indicated that exon 19, encoding the functionally important basic helix‐loop‐helix domain, was included in the deleted segment in addition to exon 20. We postulate that the TCF12 microdeletion is responsible for this patient's intellectual deficiency and facial phenotype. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Clinical genetics of craniosynostosis

“…Two follow-up studies have confirmed the importance of TCF12 mutations in coronal craniosynostosis, both in the context of familial mutations [37], and in a more general screen of craniosynostosis [29]. Given the haploinsufficiency mechanism of TCF12 mutations, heterozygous deletions are also expected to be pathogenic and this has been confirmed in two reports [38, 39]. At present, diagnostic labs rely on DNA sequencing to test TCF12 , pointing to the need for a dedicated diagnostic method such as multiplex ligation-dependent probe amplification (MLPA) to detect TCF12 deletions.…”

Molecular mechanisms underlying nuchal hump formation in dolphin cichlid, Cyrtocara moorii

“…The potential role of dlx5a in development and morphogenesis of non-skeletal craniofacial tissues in fish has not been investigated so far. The second transcription factor, tcf12 , encodes another member of bHLH E-protein family and plays role in cranio-skeletal development; particularly in the morphogenesis of the frontal bone and cranial vault thickening in mammals 82–84 . Similar to dlx5a , the potential role of tcf12 in development and morphogenesis of non-skeletal craniofacial tissues has yet to be studied in fish.…”

Genetic advances in craniosynostosis

“…Although 81% of the individuals with TCF12 mutations presented with apparent cNCS, some of the affected individuals had developmental delays and dysmorphic features overlapping with the Saethre-Chotzen syndrome [Sharma et al, 2013]. More recently, the phenotypic spectrum of TCF12 mutations has been extended to include possible facial and limb anomalies, and intellectual disability [Di Rocco et al, 2014; Le Tanno et al, 2014; Paumard-Hernandez et al, 2015; Piard et al, 2015]. Based on these observations, it is reasonable to recommend TCF12 testing for all patients with cCS, with or without associated anomalies.…”