A novel exomal ATRX mutation with preferential transmission to offspring: A case report and review of the literature for transmission ratio distortion in ATRX families
| Autor: | Davide Colavito, Anna K. Naumova, Mariano Stabile, Anna Flavia Rispoli, Marina C. Ingenito, Elda Del Giudice |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proband Male Cancer Research Heterozygote X-linked Nuclear Protein SNF domain of ATRX Offspring X-linked mental disability Pedigree chart Biology Biochemistry 03 medical and health sciences Exon 0302 clinical medicine Gene Frequency Intellectual Disability Genetics Humans Sibling Allele Molecular Biology ATRX Alleles transmission ratio distortion DNA Helicases Nuclear Proteins Articles Exons Pedigree 030104 developmental biology Phenotype Oncology ATRX mutation 030220 oncology & carcinogenesis Mutation (genetic algorithm) Mutation Molecular Medicine Female |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | The present case report describes an Italian family with three affected probands, who exhibited serious mental disability, which has not been associated with other anomalies, except with slight facial dysmorphism. Molecular multigenic analysis for intellectual disability identified a previously unreported variant, p.Ile1765Met (c.5295C>G) in the SNF domain of the ATRX protein (in exon 24). The identified mutation was found in a hemizygous state in all three affected probands and in a heterozygous state in the asymptomatic mother and the female sibling. With respect to the phenotypic similarities found in the patients with those described in previous studies, the consistency in the mode of inheritance and segregation of the mutation, the variant reported in the present case report may be considered as 'likely pathogenic'. To investigate the hypothesis that the preferential transmission of the ATRX mutation observed in this family reflected a general trend, a meta‑analysis into the segregation of ATRX mutations from published pedigrees, following allelic transmission from mothers who are heterozygous carriers to their offspring, was performed. A preferential transmission of the mutant allele to male offspring (58% of males inherited the mutant allele) was found; however, the bias was not statistically significant (P=0.29; χ2 test). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|