Molecular characteristics
Hereditary mucoepithelial dyspasia is caused by a mutation (change in the genetic material) in the SREBF1gene. Most patients tested to date carry an identical mutation identified as c.1579C>T, p.Arg527Cys. However, a few different mutations have also been recognized in other patients.
A gene (i.e. a small piece of our genetic code or DNA) is an instruction to assemble a sequence of several amino acids in the correct order to produce a protein, which is a structure essential for the formation and proper functioning of our body. If you think about the SREBF1gene as a sequence of letters in a sentence, which code for words, this specific SREBF1genetic variant is a change of a single letter (C) for another letter (T), resulting in a change of an amino acid (Arg) for another amino acid (Cys) in the protein. This genetic change disrupts the information encoded by SREBF1, which becomes non-readable.
The SREBF1gene is essential for lipid metabolism, an essential mechanism for proper development of structures such as skin, hair, and mucosae. Thus, it is thought that the disturbance of this process may result in the patient’s anomalies observed in skin, hair and mucosae.
What is needed to confirm the diagnosis of hereditary mucoepithelial dysplasia?
The diagnosis of hereditary mucoepithelial dysplasia is confirmed by performing genetic testing in an affected individual, which enables the detection of a disease-causing change in the SREBF1gene.
There are two possible strategies to identify a SREBF1change:
• If the patient’s characteristics raise the suspicion of hereditary mucoepithelial dysplasia, only the DNA sequence corresponding to the site of the recurrent mutation in SREBF1gene (known as exon 8) will be analysed using a technique known as Sanger sequencing;
• If exon 8 has no mutations, the rest of the SREBF1gene will be analysed, also by Sanger sequencing.
• 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 SREBF1gene that is not present in the healthy parents (i.e. a “de novo”change).
SREBF1