The SLC9A7-related variant (p.L515F) is a missense mutation that is pathogenic. The mutation causes a replacement of one of the amino acids in the protein with a different amino acid that causes a subtle change in the structure of the protein. This change alters the ability of the protein to function normally. The protein that is produced from the SLC9A7 gene is located in one of the intracellular organelles (the Golgi) of the cell. The SLC9A7p.L515F variant alters the pH (acid-base) balance in the Golgi that is responsible for modifying and secreting proteins involved in multiple cell functions. Patients may be confirmed to have defects in protein modification using advanced biochemical techniques.
The clinical consequences of other SLC9A7variants are unknown and remain to be investigated.
What is needed to confirm the diagnosis of SLC9A7-related disorder?
The diagnosis of SLC9A7-related disorder is confirmed by performing genetic testing in an affected individual, which enables the detection of a disease-causing change in the SLC9A7gene.
There are two possible strategies to identify a SLC9A7change:
• If the individual’s characteristics are not sufficient to raise the suspicion of SLC9A7-related syndrome (for example, because they overlap with the characteristics observed in other genetic disorders), the DNA sequence of multiple genes, including SLC9A7, will be analysed using a multi-gene panel or exome sequencing.
• If the individual’s characteristics raise the suspicion of SLC9A7-related disorder, only the DNA sequence of the SLC9A7gene 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 SLC9A7gene that is not present in the healthy parents (i.e. a “de novo” change).
SLC9A7