![]() 11, 12, 13, 14, 15, 16, 17, 18 This gene codes for a protein of at least 1411 amino acids, treacle, which is a nucleolar phosphoprotein that travels between nucleolus and cytoplasm. 10 Patients with TCS were found to be heterozygous for mutations in the TCOF1 gene, which is located in 5q32–q33.1. 8, 9 This complex pattern of malformation is thought to be caused by impaired development of structures derived from the first and second branchial arches between the 5th and 8th week of embryonic development. ![]() 7 TCS is characterized by bilateral downward slanting palpebral fissures, frequently accompanied by colobomas of the lower eyelid and a paucity of eyelashes medial to the defect, abnormalities of the external ears, atresia of external auditory canal and bilateral conductive hearing loss, hypoplasia of the zygomatic complex and mandible, and cleft palate. 5, 6 More than 60% of patients have no positive family history. 4 TCS is diagnosed in 1/50 000 live births. 3 The synonym Franceschetti–Klein syndrome is preferred in many German-speaking countries because of the excellent overview by Franceschetti and Klein (1949). 1 However, there are two earlier reports by Thomson (1846) 2 and Berry (1889). ![]() Treacher Collins syndrome (TCS, MIM 154500) is an autosomal dominant mandibulofacial dysostosis. The difficulties in genetic counselling, especially diagnosis of family members with a mild phenotype, are described. Based on these findings, minimal diagnostic criteria were defined: downward slanting palpebral fissures and hypoplasia of the zygomatic arch. This suggests that modifying factors are important for phenotypic expression. Some mutation carriers, parents of typically affected patients, are so mildly affected that the diagnosis might be overlooked clinically. Inter- and intrafamilial variation is wide. There is no overt genotype–phenotype correlation except that conductive deafness is significantly less frequent in patients with mutations in the 3′ part of the open reading frame. No mutation was identified in the remaining eight patients with unequivocal diagnosis of TCS and 10 further patients, in whom the referring diagnosis of TCS was clinically doubtful. ![]() In 36 patients with a clinically unequivocal diagnosis of TCS, we detected 28 pathogenic mutations, including 25 novel alterations. A total of 27 coding exons of TCOF1 and adjacent splice junctions were analysed by direct sequencing. To define the range of phenotypic expression in Treacher Collins syndrome (TCS Franceschetti–Klein syndrome), we performed mutation analysis in the TCOF1 gene in 46 patients with tentative diagnosis of TCS and evaluated the clinical data, including a scoring system. ![]()
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