OFD1

About 100 mutations in the OFD1 gene have been found in people with oral-facial-digital syndrome type I, which is the most common form of the disorder. These mutations include changes in single DNA building blocks (base pairs) and larger deletions of genetic material from the OFD1 gene. Most of these genetic changes lead to the production of an abnormally short, nonfunctional version of the OFD1 protein. It is unclear how a shortage of functional OFD1 protein leads to the specific features of oral-facial-digital syndrome type I. However, studies suggest that a lack of this protein prevents the normal formation of cilia, which affects the development of many tissues and organs.

Mutations in the OFD1 gene can also cause several other disorders with features that overlap with those of oral-facial-digital syndrome (described above), such as Joubert syndrome. This disorder is characterized by particular brain abnormalities, weak muscle tone (hypotonia), delayed development, unusual eye movements, and breathing problems.

The OFD1 mutations responsible for Joubert syndrome lead to the production of an abnormally short version of the OFD1 protein. However, studies suggest that these mutations result in a somewhat longer protein than the mutations that cause oral-facial-digital syndrome. This protein may retain some of its usual function in cilia. The abnormal protein probably disrupts the development or function of cilia in some way, although it is unclear how these changes result in the signs and symptoms of Joubert syndrome.

MedlinePlus Genetics provides information about Primary ciliary dyskinesia

MedlinePlus Genetics provides information about Simpson-Golabi-Behmel syndrome

At least one OFD1 gene mutation has been found in a family with a form of X-linked intellectual disability. Individuals with this condition have severe intellectual disability, an unusually large head size (macrocephaly), and breathing problems.

This OFD1 gene mutation leads to the production of an abnormally short version of the OFD1 protein. However, the altered protein appears to be longer than the abnormal proteins involved in oral-facial-digital syndrome (described above). This protein may retain some of its usual function in cilia. The abnormal protein probably disrupts the development or function of cilia in some way, although it is unclear how these changes result in the signs and symptoms of X-linked intellectual disability.