Neuropediatrics 2021; 52(02): 138-141
DOI: 10.1055/s-0040-1715633
Short Communication

The Variable Expression of a Novel MBD5 Gene Frameshift Mutation in an Italian Family

1  Inter-departmental Program for Molecular Diagnosis and Characterization of Pathogenic Mechanisms of Rare Genetic Diseases, Azienda Ospedaliero Universitaria Senese, Siena, Italy
2  Clinical Genetics, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy
,
Lucia Galli
2  Clinical Genetics, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy
1  Inter-departmental Program for Molecular Diagnosis and Characterization of Pathogenic Mechanisms of Rare Genetic Diseases, Azienda Ospedaliero Universitaria Senese, Siena, Italy
,
Maja Rossi
3  Molecular Diagnostic Laboratory, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy
,
Ambra Cortesi
3  Molecular Diagnostic Laboratory, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy
,
Marta Mazzi
4  Pathophysiology of Human Reproduction, ASL Toscana Sudest, Ospedale della Misericordia, Grosseto, Italy
,
Ettore Caterino
5  Neuropsychiatry Unit, ASL Toscana Sudest, UFSMIA Zona Amiata Grossetana, Grosseto, Italy
› Author Affiliations

Abstract

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) 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 MBD5 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 MBD5 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.

Supplementary Material



Publication History

Received: 13 December 2019

Accepted: 26 May 2020

Publication Date:
29 December 2020 (online)

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