Centre de Génomique Humaine - Faculté de Médecine et de Pharmacie- Université Mohamed V, Rabat, Morocco.
Centre de Génomique Humaine - Faculté de Médecine et de Pharmacie- Université Mohamed V, Rabat, Morocco; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.
Eur J Med Genet. 2020 Jul;63(7):103951. doi: 10.1016/j.ejmg.2020.103951. Epub 2020 May 18.
Genetic factors represent a considerable part of the etiologies of intellectual disability; however, the identification of causal genetic anomaly has long been complicated by the great clinical and genetic heterogeneity of this type of disease. With advances in next-generation sequencing technologies and functional studies, the identification of genes involved in intellectual development has led to more accurate diagnostics and better understanding of the underlying biological pathways.
We report on the case of two Moroccan siblings presenting mild intellectual disability with minimal dysmorphic features in which whole exome sequencing analysis revealed homozygous mutation in the METTL23 gene. Mutations in this gene have been reported to cause autosomal recessive mild intellectual disability but the association with dysmorphic features remains controversial.
Hereby, we highlight the similarity of the dysmorphic traits and the characteristic facial features in patients with METTL23-related intellectual disability, suggesting the consideration of a distinct clinical entity associating mild intellectual deficiency with specific facial dysmorphy for an efficient diagnosis orientation and a better phenotype-genotype correlation in intellectual disability disorders.
遗传因素在智力障碍的病因中占相当大的比例；然而，由于这种疾病的临床表现和遗传异质性很大，因此确定因果遗传异常一直很复杂。随着下一代测序技术和功能研究的进展，参与智力发育的基因的鉴定导致了更准确的诊断和对潜在生物学途径的更好理解。
我们报告了两例摩洛哥同胞的病例，他们表现为轻度智力障碍，仅有轻微的畸形特征，全外显子组测序分析显示 METTL23 基因纯合突变。该基因的突变已被报道可导致常染色体隐性轻度智力障碍，但与畸形特征的关联仍存在争议。
在此，我们强调了 METTL23 相关智力障碍患者的畸形特征和特征性面部特征的相似性，表明对于轻度智力缺陷伴特定面部畸形的明确临床实体的考虑，对于有效的诊断方向和智力障碍疾病中的表型-基因型相关性更好。
