autosomal-dominant pattern. Mutations in<unk> , POLR1C, or POLR1D genes can cause<unk> .<unk>  gene mutations are the most common cause of the disorder, with POLR1C and POLR1D gene mutations causing an additional 2% of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. The<unk> , POLR1C, and POLR1D genes code for proteins which play important roles in the early development of bones and other tissues of the face. Mutations in these genes reduce the production of rRNA, which may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. It is unclear why the effects of a reduction in rRNA are limited to facial development. Mutations in<unk>  and POLR1D cause the autosomal dominant form of<unk><unk> , and mutations in POLR1C cause the autosomal recessive form.<unk> <unk>  is the primary gene associated with<unk> , a mutation in this gene being found in 90–95% of the individuals with<unk> . However, in some individuals with typical symptoms of<unk> , mutations in<unk>  have not been found. Investigation of the DNA has resulted in the identification of the kind of mutations found in<unk> . The majority of mutations are small deletions or insertions, though splice site and missense mutations also have been identified. Mutation analysis has unveiled more than 100 disease-causing mutations in<unk> , which are mostly family-specific mutations. The only recurrent mutation accounts for about 17% of the cases.<unk>  is found on the 5th chromosome in the 5q32 region. It codes for a relatively simple nucleolar protein called treacle, that is thought to be involved in ribosome assembly. Mutations in<unk>  lead to haploinsufficiency of the treacle protein. Haploinsufficiency occurs when a diploid organism has only one functional copy of a gene, because the other copy is inactivated by a mutation. The one normal copy of the gene does not produce enough protein, causing disease. Haploinsufficiency of the treacle protein leads to a depletion of the neural crest cell precursor, which leads to a reduced number of crest cells migrating to the first and second pharyngeal arches. These cells play an important role in the development of the craniofacial appearance, and loss of one copy of treacle affects the cells' ability to form the bones and tissues of the face. Other mutations POLR1C and POLR1D mutations are responsible for a minority of cases of<unk><unk> . POLR1C is found on chromosome 6 at position 6q21.2 and POLR1D is found on chromosome 13 at position 13q12.2. Those genes code for a protein subunits shared between RNA polymerase I and III. Both of these polymerases are important for ribosome biogenesis.
Treacher Collins syndrome
Miller syndrome
ATR-16 syndrome
Hemifacial microsomia
ATR-X syndrome
Nager acrofacial dysostosis
LIG4 syndrome
Otocephaly