SNP Shot: Genomic Insights

6q24-related transient neonatal diabetes mellitus (TNDM) is a type of diabetes that affects newborns. In this condition, infants experience high blood sugar (hyperglycemia) due to insufficient production of insulin. Insulin is crucial for regulating blood glucose levels by facilitating the entry of glucose (a type of sugar) from the blood into cells for energy production.

Infants with 6q24-related TNDM often exhibit significantly reduced growth before birth, known as severe intrauterine growth retardation. These babies develop hyperglycemia and dehydration, typically within the first week of life. The symptoms of this diabetes are transient, meaning they diminish over time and usually resolve between 3 and 18 months of age. However, the diabetes can return, particularly during childhood illnesses or pregnancy. Notably, up to 50% of individuals with 6q24-related TNDM may eventually develop permanent diabetes mellitus later in their lives.

Some individuals with 6q24-related TNDM may also exhibit other features, including an enlarged tongue (macroglossia), an umbilical hernia (a soft bulge near the belly button), structural abnormalities affecting the brain, heart, or kidneys, low muscle tone (hypotonia), hearing loss, and delays in development.

Inheritance:

Most cases of 6q24-related TNDM are not passed down through families, especially those resulting from paternal uniparental disomy. In these instances, genetic alterations occur randomly during the formation of egg or sperm cells, or in the early stages of embryonic development. Consequently, affected individuals usually have no family history of the condition. In other instances, the genetic change responsible for 6q24-related TNDM can be inherited, such as a duplication of genetic material on the paternal chromosome 6, which can be transmitted across generations.

When 6q24-related TNDM is caused by mutations in the ZFP57 gene, it follows an autosomal recessive inheritance pattern. This means that both copies of the ZFP57 gene in each cell must have a mutation for the condition to develop. In autosomal recessive inheritance, each parent of an affected individual carries one copy of the mutated gene, but they usually do not exhibit any signs or symptoms of the condition themselves.