In this edition of "Spotlight C18 Gene", we will discuss one of the first chromosome 18 genes ever characterized:  TGIF1 .  You might think this gene was named by a researcher eager for the week-end. Perhaps so, but the initials " TGIF1 " actual stand for "TGFB-induced factor, homeobox 1". This long, complicated name simply tells us that another protein triggers the production of the TGIF1 protein product.

Of course, the function of  TGIF1 is more important than the origins of its name. It has been directly linked to one of the earliest reported features of 18p-: holoprosencephaly.  Holoprosencephaly is a type of birth defect in which the two parts of the brain do not divide as they should. Usually, the brain is separated into two halves which are connected by a band of tissue called the corpus callosum. Holoprosencephaly describes an incomplete separation of these two halves. This birth defect occurs very early in prenatal development. There are varying levels of severity. The most severe forms typically cause other visible malformations of the face and very severe medical problems. Babies with the most severe forms of holoprosencephaly usually pass away before birth or shortly afterwards. However, some babies are born with less severe forms which, in mild cases, may not be immediately obvious. In addition, some people have holoprosencephaly microforms. This means that the brain may appear to have formed normally, but there are other differences in the body's midline, such as a cleft palate, or a single tooth in the center of the mouth (single central incisor).  

The connection between 18p- and holoprosencephaly was first noted as early as the 1970's. However, it was not until the early 2000's that the responsible gene, TGIF1, was identified. Researchers studying people with isolated holoprosencephaly found changes in the TGIF1 gene.   TGIF1 is located at 3,451,591 Mb (18p11.31). Therefore, it made sense that this was the cause of holoprosencephaly in people with 18p-. However, only about 10% of people with deletions that include  TGIF1 have holoprosencephaly or any of its microforms.

The question then arises, "If many people with 18p- are missing the  TGIF1 gene, why don't  all of them have holoprosencephaly?" As it turns out, just having a missing copy of  TGIF1 is not enough to cause holoprosencephaly by itself. Some other factors, either genetic or environmental, are likely necessary. We don't fully understand all of these other factors at this time. Researchers continue to search for the a complete understanding of the underlying causes of holoprosencephaly. This research is happening both at the Chromosome 18 Clinical Research Center as well as other institutions that are dedicated to brain anomalies. In the future, we anticipate that we will continue to benefit from others' research, just as they will continue to benefit from ours!