Novel mutations of TCOF1 gene in European patients with treacher Collins syndrome

Abstract

BackgroundTreacher Collins syndrome (TCS) is one of the most severe autosomal dominant congenital disorders of craniofacial development and shows variable phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in 50.000 live births. The TCS distinguishing characteristics are represented by down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present. TCS results from mutations in the TCOF1 gene located on chromosome 5, which encodes a serine/alanine-rich nucleolar phospho-protein called Treacle. However, alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases.MethodsIn this study, the entire coding regions of the TCOF1 gene, including newly described exons 6A and 16A, were sequenced in 46 unrelated subjects suspected of TCS clinical indication.ResultsFifteen mutations were reported, including twelve novel and three already described in 14 sporadic patients and in 3 familial cases. Moreover, seven novel polymorphisms were also described. Most of the mutations characterised were microdeletions spanning one or more nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop mutation. The deletions and the insertion described cause a premature termination of translation, resulting in a truncated protein.ConclusionThis study confirms that almost all the TCOF1 pathogenic mutations fall in the coding region and lead to an aberrant protein.

Mandibulofacial dysostosis (Treacher Collins syndrome): A case report and review of literature

“…In 40%, the mutation may be inherited from the parents. [56] The present case has shown the positive family history suggesting familial mutation transfer in TCOF1 gene, which is seen in 40% of cases.…”

Ear malformations, hearing loss and hearing rehabilitation in children with Treacher Collins syndrome

“…1,2 In most cases, it is caused by a mutation in TCOF1 gene in loci 5q31.3, which encodes a nucleolar phosphoprotein ---Treacle, essential for the development of the 1st and 2nd branchial arches. 3,4 The penetrance of these mutations is complete, but its expressivity is variable. 5 In cases of complete expression of TCS, the diagnosis can be based on clinical features.…”

Repercussões Bucais da Síndrome de Treacher Collins: revisão de literatura

“…Nesse contexto, sabe-se que cerca de 40% dos acometimentos pela síndrome são de origem hereditária, enquanto outros 60% são advindos de mutação nova (10,13).…”