Genetics
Genes are the building blocks of life. They are just like recipes but instead of making a cake, genes code for proteins that have important functions in the body. FOXP1 is a specific gene found on chromosome 3 that instructs the production of the Forkhead Box P1 protein. When the gene has a change or mutation it does not function properly and the “recipe” for making the cake is changed resulting in the possibility of a variety of developmental and medical issues.
Whole exome sequencing is a single test able to identify changes or mutations in the person’s entire genetic makeup. Panel testing is able to identify changes or mutations in a subset of genes associated with a particular clinical feature (e.g., autism panel, intellectual disability panel, epilepsy panel). Mutations are most often picked up on neurodevelopmental panel tests or whole exome sequencing. In recent years both panels and whole exome sequencing has become more accessible and therefore children with developmental and or medical symptoms are being diagnosed at younger ages.
In the vast majority of FOXP1 cases, the mutation in the gene is called a de novo mutation which means that neither parent has the mutation; this de novo mutation most likely occurred spontaneously during early fetal development. This can be confirmed by genetic testing of the parents. In the case of a de novo mutation, the probability of the parents having another child with the same mutation is very low, though the affected child could as an adult pass on the mutation.
Gene Mutation
In the alphabet, different letters can be combined to produce useful and
meaningful words – but only if the letters are put together in the correct way. The same works for DNA. Certain nucleotides (the base unit of DNA) whether it is adenine (A), thymine (T), cytosine (C), or guanine (G) can be arranged in a specific manner to form the FOXP1 gene, which in turn encodes a specific protein. A missense mutation is when there is a single DNA nucleotide switch in the gene. Sometimes such a change is silent and has no effect on the protein encoded by the DNA. Other changes result in an amino acid change in the protein the gene codes for, which sometimes can profoundly change the way the protein functions
Missense Mutation
A missense mutation is when there is a single DNA nucleotide switch in the gene. Sometimes such a change is silent and has no effect on the protein encoded by the DNA. Other changes result in an amino acid change in the protein the gene codes for, which sometimes can profoundly change the way the protein functions.
Nonsense and Frameshift Mutations
Like a missense mutation, a nonsense mutation also involves a single alteration in the DNA. However, in the case of a nonsense mutation, this single change results in the production of a stop codon, (stop codons signal the end of the protein coding sequencing), there by terminating protein synthesis (process in which cells make proteins) prematurely. The protein may not be made at all, or a shortened version of the protein may be made. Similarly, frameshift mutations arise when one or a small number of nuclootides are deleted or inserted, causing the 3-letter "words" of the gene to come out of alignment; this kind of mutation can introduce a premature stop codon, or can cause all the "downstream" words to be misread. Either outcome can result in major disruption to the way the protein functions.
What is FOXP1 Syndrome?
FOXP1 syndrome is considered a rare disease that is caused by a mutation or change to the FOXP1 gene. The gene is located on chromosome 3 and includes the instructions or “recipe” for making the Forkhead BOXP1 protein. As a member of a family of transcription factors, it is vital in regulating the expression of other genes. FOXP1 controls when and how specific genes affect the development of the nervous system, along with many other systems. When a gene like FOXP1 does not function properly it can lead to a wide range of developmental delays and medical needs.
What causes FOXP1 Syndrome?
Chromosomes are the structures that carry an individual’s genetic information. This information is encoded by units called genes, which can be thought of as long words made up of strings of 4 different “letters” (A, G, T, and C). Genes are arranged along the chromosome like words in a sentence. In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46 chromosomes. Twenty-two of these pairs (autosomes) look the same in males and females. The 23rd pair (sex chromosomes) differs between sexes. Humans usually have two copies of every gene on the autosomes, including FOXP1.
FOXP1 syndrome is caused by genetic lesions (mutations) of the FOXP1 gene.
These include a swap of a single letter or loss or gain of a few letters on one copy of the gene, as well partial or total deletions of one copy of the gene. The disorder is referred to as "autosomal dominant" because mutations of a single copy of FOXP1 are enough for a person to be affected. FOXP1 mutations typically arise
spontaneously in affected individuals (that is, not inherited), and are therefore
referred to as “de novo” mutations. Because the parents would typically have two
normal copies of the FOXP1 gene, there is a very small chance to have a second
child with FOXP1 syndrome.
How common are FOXP1 gene mutations?
FOXP1 mutations are rare, but more and more cases are being identified as genetic testing becomes more widespread. There are several online parent groups that operate in difference languages on Facebook. Each year hundreds of new cases are indentured around the globe. There are likely many more people carrying mutations in the gene who have not yet been diagnosed.