Inter-departmental Program for Molecular Diagnosis and Characterization of Pathogenic Mechanisms of Rare Genetic Diseases, Azienda Ospedaliero Universitaria Senese, Siena, Italy.
Clinical Genetics, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy.
Neuropediatrics. 2021 Apr;52(2):138-141. doi: 10.1055/s-0040-1715633. Epub 2020 Dec 29.
Haploinsufficiency of the methyl-CpG-binding domain protein 5 () gene is reported as a cause of an autosomal dominant type of cognitive disability (MRD1) and autism spectrum disorder through large deletions involving multiple genes or point mutations, ultimately leading to haploinsufficiency in both cases. However, relatively few reports have been published on the phenotypical spectrum resulting from point mutations.We report here on a novel heterozygous frameshift variant in the gene [c.2579del; p.(Lys860Argfs*11)] in a family in which the typical signs associated with pathogenic variants were expressed with different degrees of severity in the clinical presentation of the carrier individuals.Our findings, adding a novel mutation to the mutational spectrum, further support the relevance of the gene as one of the main molecular mechanisms involved in the pathogenesis of intellectual disability and contribute to the characterization of the genotype-phenotype correlations.
据报道，甲基-CpG 结合域蛋白 5 () 基因的单倍剂量不足是一种常染色体显性认知障碍 (MRD1) 和自闭症谱系障碍的原因，这种疾病是通过涉及多个基因的大片段缺失或点突变引起的，最终导致两种情况下的单倍剂量不足。然而，由于点突变导致的表型谱相对较少有报道。我们在此报告一个新的杂合移码变异 [c.2579del;p.(Lys860Argfs*11)] 在一个家系中，该家系中与致病性变异相关的典型体征在携带者个体的临床表现中以不同程度的严重程度表达。我们的发现，在突变谱中增加了一个新的突变，进一步支持了 基因作为涉及智力障碍发病机制的主要分子机制之一的相关性，并有助于基因型-表型相关性的特征描述。
