1 - Centro Hospitalar Universitário de Lisboa Central, Serviço de Genética Médica, Lisboa, Portugal
2 - CGPP – Centro de Genética Preditiva e Preventiva, IBMC – Instituto de Biologia Molecular e Celular, i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- European Human Genetics Conference 2022, reunião internacional, sob a forma de poster
Background/Objectives: TCF12 gene encodes transcription factor 12 (tcf12), a member of the basic helix-loop-helix (bHLH), and plays a key role in neurogenesis, mesoderm formation, and cranial suture development. TCF12 haploinsufficiency results in coronal craniosynostosis type 3 (CRS3, #615314) and hypogonadotropic hypogonadism 26 (#619718). Several cases of CRS3 presented with other comorbidities such neurodevelopmental impairment, dysmorphims and other congenital anomalies.
Methods: We report a new patient with a likely pathogenic variant in TCF12 gene aiming to further expand its clinical spectrum.
Results: A 30-year-old female was first referred to our outpatient genetic department at 16-years-old with a central nervous system malformation (focal cortical dysplasia with left-side frontal polymicrogyria), nystagmus, right hemiparesis, epilepsy, hearing loss and intellectual disability. At our observation, she showed low anterior hairline, thin upper lip, and a prominent chin. Extensive investigation was performed with normal karyotype, FRAXA, metabolic investigation, microarray analysis. Exome sequencing identify a de novo heterozygous variant in TCF12 (NM_207036.1):c.1453C>T (p.(Arg485*)), classified as likely pathogenic, previously described as a cause of CRS3.
Conclusion: Although, our patient does not have a craniosynostosis, this result can potentially explain the phenotype and be clinically relevant. We propose that TCF12 could be responsible for other craniofacial abnormalities and neurodevelopmental disorders. It is important to note that genetic research suggests that mutations in regulatory elements of genes can cause developmental defects. Therefore, more investigation is necessary to understand the role of tcf12 as transcriptional.
Palavras Chave: TCF12 gene