Title Donor splice site variant in SLC9A6 causes Christianson syndrome in a Lithuanian family: a case report /
Authors Petraitytė, Gunda ; Mikštienė, Violeta ; Siavrienė, Evelina ; Cimbalistienė, Loreta ; Maldžienė, Živilė ; Rančelis, Tautvydas ; Vaitėnienė, Evelina Marija ; Ambrozaitytė, Laima ; Dapkūnas, Justas ; Dzindzalieta, Ramūnas ; Pranckevičienė, Erinija ; Kučinskas, Vaidutis ; Utkus, Algirdas ; Preikšaitienė, Eglė
DOI 10.3390/medicina58030351
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Is Part of Medicina.. Kaunas; Basel : LSMU ; MDPI AG. 2022, vol. 58, no. 3, art. no. 351, p. [1-11].. ISSN 1010-660X. eISSN 1648-9144
Keywords [eng] SLC9A6 ; donor splice site variant ; Christianson syndrome ; cDNA analysis ; protein modelling
Abstract [eng] 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.
Published Kaunas; Basel : LSMU ; MDPI AG
Type Journal article
Language English
Publication date 2022
CC license CC license description