Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.

Treacher Collins syndrome (TCS) is associated with an abnormal differentiation of the first and second pharyngeal arches during fetal development. This causes mostly craniofacial deformities, which require numerous corrective surgeries. TCS is an autosomal dominant disorder and it occurs in the general population at a frequency of 1 in 50,000 live births. The syndrome is caused by mutations in the TCOF1 gene, which encodes the serine/alanine-rich protein named Treacle. Over 120 mutations of the TCOF1 gene responsible for TCS have been described. About 70% of recognized mutations are deletions, which lead to a frame shift, formation of a termination codon, and shortening of the protein product of the gene. Herewith, a new heterozygotic insertion, c.484_668ins185bp, was described in two monozygotic twin sisters suffering from TCS. This mutation was absent in their father, brother, and uncle, indicating a de novo origin. The insertion causes a shift in the reading frame and premature termination of translation at 167 aa. The novel insertion is the longest ever found in the TCOF1 gene and the only one found among monozygotic twin sisters.

Here we describe three novel TCOF1 mutations found in unrelated patients with Treacher Collins syndrome. These mutations include one deletion, NM_001135243.2:c.2604_2605delAG (p.Gly869Glufs*3), and two substitutions, NM_001135243.2:c.2575C>T (p.Gln859*) and NM_001135243.2:c.4111G>T (p.Glu1371*). These mutations cause shortening of a protein called Treacle in patients with features typical of TCS. Continuous identification of new mutations is important to expand the mutation base, which is helpful in the diagnosis of both patients and their families

Novel deletion Treacher Collins syndrome Słowa kluczowe: TCOF1 Nowa delecja Zespół Treachera Collinsa a b s t r a c t Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development. The syndrome is characterized by a similar phenotype: micrognathia, microtia, midface hypoplasia, cleft lip and palate. The estimated incidence rate is 1/50 000 live births. Treacher Collins syndrome is mostly caused by mutations in the TCOF1 gene, which encodes the serine/alanine-rich protein Treacle. TCS can also be caused by mutations in the POLR1C and POLR1D genes. About 70% of recognized mutations of the TCOF1 gene in TCS patients are deletions, which lead to formation of a termination codon and shortening of the protein. The aim of the study was to search for mutations in TCOF1gene causing a Treacher Collins syndrome. Examined DNA was isolated from peripheral blood leukocytes of the male patient born at 38 weeks of gestation and his healthy parents. The PCR products were subjected to MSSCP analysis. The PCR products were purified on the DNA GelOut columns followed by direct sequencing. A novel, heterozygous deletion c.1978delC was detected in one patient with typical facial symptoms of Treacher Collins syndrome. The patient's parents were tested and no mutation was observed, indicating de novo origin of the examined mutation. The c.1978delC deletion causes premature termination of translation at 677aa. The finding will facilitate precise diagnosis of the patient and will extend knowledge on the pathogenesis of TCS.

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