Individuals with Christianson syndrome possess a range of de novo (new) or inherited pathogenic mutations in the SLC9A6gene (>100 mutations described to date).
The SLC9A6gene produces a protein that helps regulate the acid-base (pH) balance in small membranous vesicles inside cells. These vesicles deliver certain types of proteins to the cell surface of neurons as well as other cell types that are thought to be important for brain development and function. Abnormalities of the gene affect the way some proteins are modified and transported within the cell.
Usually, SLC9A6-related conditions are caused by a single spelling variation in the gene, which means the message is not read or received properly. In some individuals, a section of the chromosome that includes the SLC9A6gene (called Xq26.3) is missing. This is called a deletion.
SLC9A6-related conditions are genetic conditions. This means that the condition was not caused by anything the mother or father did before the baby was conceived, during pregnancy or birth, or after the baby was born. SLC9A6-related conditions are rare, affecting with less than 1000 individuals in the United States. As the disorder is X-linked it may often affect more than one child and be inherited from an unaffected mother.
The clinical consequences of many SLC9A6variants are unknown and remain to be investigated.
What is needed to confirm the diagnosis of SLC9A6-related syndrome?
The diagnosis of SLC9A6-related syndrome is confirmed by performing genetic testing in an affected individual, which enables the detection of a disease-causing change in the SLC9A6 gene.
There are two possible strategies to identify a SLC9A6change:
• If the individual’s characteristics are not sufficient to raise the suspicion of SLC9A6-related syndrome (for example, because they overlap with the characteristics observed in other genetic disorders), the DNA sequence of multiple genes, including SLC9A6, will be analysed using a multi-gene panel or exome sequencing.
• If the individual’s characteristics raise the suspicion of SLC9A6-related syndrome, only the DNA sequence of the SLC9A6gene will be analysed.
The genetic testing can be arranged by a clinical geneticist and involves the collection of a sample of blood or saliva from the affected individual (and eventually the parents). Analysing the DNA of the patient and comparing it with the parents’ DNA may facilitate the detection of a disease-causing change in the SLC9A6gene that is not present in the healthy parents (i.e. a “de novo” change).
SLC9A6