Donor Splice Site Variant in SLC9A6 Causes Christianson Syndrome in a Lithuanian Family: A Case Report

Autor: Gunda Petraitytė, Violeta Mikštienė, Evelina Siavrienė, Loreta Cimbalistienė, Živilė Maldžienė, Tautvydas Rančelis, Evelina Marija Vaitėnienė, Laima Ambrozaitytė, Justas Dapkūnas, Ramūnas Dzindzalieta, Erinija Pranckevičienė, Vaidutis Kučinskas, Algirdas Utkus, Eglė Preikšaitienė
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Medicina, Vol 58, Iss 3, p 351 (2022)
Druh dokumentu: article
ISSN: 1648-9144
1010-660X
DOI: 10.3390/medicina58030351
Popis: Background and Objectives: The pathogenic variants of SLC9A6 are a known cause of a rare, X-linked neurological disorder called Christianson syndrome (CS). The main characteristics of CS are developmental delay, intellectual disability, and neurological findings. This study investigated the genetic basis and explored the molecular changes that led to CS in two male siblings presenting with intellectual disability, epilepsy, behavioural problems, gastrointestinal dysfunction, poor height, and weight gain. Materials and Methods: Next-generation sequencing of a tetrad was applied to identify the DNA changes and Sanger sequencing of proband’s cDNA was used to evaluate the impact of a splice site variant on mRNA structure. Bioinformatical tools were used to investigate SLC9A6 protein structure changes. Results: Sequencing and bioinformatical analysis revealed a novel donor splice site variant (NC_000023.11(NM_001042537.1):c.899 + 1G > A) that leads to a frameshift and a premature stop codon. Protein structure modelling showed that the truncated protein is unlikely to form any functionally relevant SLC9A6 dimers. Conclusions: Molecular and bioinformatical analysis revealed the impact of a novel donor splice site variant in the SLC9A6 gene that leads to truncated and functionally disrupted protein causing the phenotype of CS in the affected individuals.
Databáze: Directory of Open Access Journals
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