A Brief Analysis on Clinical Severity of Mandibulofacial Dysostosis Guion-Almeida Type

Abstract

Objective Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype–phenotype correlation in MFDM. Methods Forty articles comprising 156 patients were evaluated. The genotype–phenotype correlation was analyzed using a chi-square or Fisher's exact test. Results The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype–phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. Conclusion Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype–phenotype relationships in this disease.

Atypical mandibulofacial dysostosis with microcephaly diagnosed through the identification of a novel pathogenic mutation in EFTUD2

“…These include missense mutations, nonsense mutations, insertions, small deletions/duplications, splice site mutations and large gene deletions. The mutations are found in the exonic (67.7%) or intronic (31.6%) regions, with no mutation hotspot found within EFTUD2 (Ulhaq et al., 2024 ). Most of the mutations are predicted to result in haploinsufficiency of EFTUD2 .…”

“…Currently, there are only approximately 150 reported cases of MFDM that have been confirmed to carry EFTUD2 mutations and most of these are individuals of European descent. There are still limited numbers of patients with an Asian background (Ulhaq et al., 2024 ). The phenotypic and genotypic spectrum of MFDM needs to be expanded to fully understand the clinical characteristics and pathogenesis.…”

The feedback loop of EFTUD2/c-MYC impedes chemotherapeutic efficacy by enhancing EFTUD2 transcription and stabilizing c-MYC protein in colorectal cancer

“…EFTUD2 is an essential component of the spliceosome complex, acting as a character that shears pre-mRNAs to produce mature mRNAs [12] . EFTUD2 has been implicated in several diseases, including Mandibulofacial Dysplasia [13] , Guion-Almeida Type (MFDGA) [14] , Alzheimer's disease [15] , and various cancers [16][17][18] . Signi cantly, recent studies have revealed a close correlation between EFTUD2 and digestive system diseases, particularly liver cancer, where it exhibits signi cant upregulation.…”