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2019

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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MUTATIONS IN CTC1, ENCODING CONSERVED TELOMERE MAINTENANCE COMPONENT 1, CAUSE COATS PLUS

Anderson Beverley1, José Pedro Vieira2.

1 - Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, Manchester, UK;
2 - Department of Neurology, Hospital Dona Estefânia, Centro Hospitalar Lisboa Central, E.P.E.

- Nature Genetics 2012; 44: 338-342.

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis thaliana CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosiscongenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the a-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-a primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Keywords: CTC1 mutations, coats plus.