Which gene variant is primarily associated with Pendred Syndrome?

Pendred Syndrome is primarily associated with a variant in the SLC26A4 gene. This gene encodes a protein that is crucial for the transport of anions, particularly iodide, in the inner ear and thyroid. In Pendred Syndrome, mutations in SLC26A4 lead to dysfunction in the inner ear, resulting in hearing loss, as well as potential thyroid dysfunction due to impaired iodide transport, which can cause goiter.

The other genes listed do not play a significant role in Pendred Syndrome. For instance, CISD2 is associated with Wolfram Syndrome, COL4A1 relates to various conditions affecting collagen, particularly in the kidneys and brain, and TCOF1 is primarily linked to Treacher Collins Syndrome, which does not involve any characteristics of Pendred Syndrome. Understanding the specific role of SLC26A4 in the pathology of Pendred Syndrome is crucial for genetic counseling, where accurate identification of the causative gene has implications for diagnosis, management, and family planning for affected individuals and their relatives.