The TFE3gene encodes a transcription factor, a type of protein, with key roles in developmental pathways and embryonic stem cell differentiation. It travels to the nucleus to promote the reading of target genes involved in the production of lysosomes. The lysosomes are important parts of the cell in charge of breaking down excess or worn-out cell parts. Lately they have been found to be key regulators of a wide range of cellular functions such as metabolic signaling.
All the variants in TFE3gene reported to date are de novo, which means they are not inherited from the parents.
The diagnosis of TFE3-associated neurodevelopmental disorder is confirmed by performing genetic testing in an affected individual, which enables the detection of a disease-causing change in the TFE3gene.
There are two possible strategies to identify a TFE3change:
• If the individual’s characteristics are not sufficient to raise the suspicion of TFE3-associated neurodevelopmental disorder (for example, because they overlap with the characteristics observed in other genetic disorders), the DNA sequence of multiple genes, including TFE3, will be analyzed using a multi-gene panel or exome sequencing.
• If the individual’s characteristics raise the suspicion of TFE3-associated neurodevelopmental disorder, only the DNA sequence of the TFE3gene will be analyzed.
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). Analyzing the DNA of the patient and comparing it with the parents’ DNA may facilitate the detection of a disease-causing change in the TFE3gene that is not present in the healthy parents (i.e. a “de novo” change).
TFE3