Donor Splice Site Variant in <i>SLC9A6</i> Causes Christianson Syndrome in a Lithuanian Family: A Case Report
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
Affiliations
Gunda Petraitytė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Violeta Mikštienė
Biobank of the Lithuanian Population and Rare Disorders, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania
Evelina Siavrienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Loreta Cimbalistienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Živilė Maldžienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Tautvydas Rančelis
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Evelina Marija Vaitėnienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Laima Ambrozaitytė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Justas Dapkūnas
Department of Bioinformatics, Institute of Biotechnology, Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania
Ramūnas Dzindzalieta
Biobank of the Lithuanian Population and Rare Disorders, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania
Erinija Pranckevičienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Vaidutis Kučinskas
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Algirdas Utkus
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
Eglė Preikšaitienė
Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-08661 Vilnius, Lithuania
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.
