Mutations in the telomere capping complex in bone marrow failure and related syndromes.
Dyskeratosis congenita and its variants have overlapping phenotypes with many disorders including Coats plus, and their underlying pathology is thought to be one of defective telomere maintenance. Recently, biallelic CTC1 mutations have been described in patients with syndromes overlapping Coats plus. CTC1, STN1 and TEN1 are part of the telomere-capping complex involved in maintaining telomeric structural integrity. Based on phenotypic overlap we screened 73 genetically uncharacterized patients with dyskeratosis congenita and related bone marrow failure syndromes for mutations in this complex. Biallelic CTC1 mutations were identified in 6 patients but none in either STN1 or TEN1. We have expanded the phenotypic spectrum associated with CTC1 mutations and report that intracranial and retinal abnormalities are not a defining feature, as well as showing that the effect of these mutations on telomere length is variable. The study also demonstrates the lack of disease-causing mutations in other components of the telomere-capping complex.
Centre for Paediatrics, Barts, UK. a.walne@qmul.ac.uk
Amanda J
AJ
Walne
Tanya
T
Bhagat
Michael
M
Kirwan
Cyril
C
Gitiaux
Isabelle
I
Desguerre
Norma
N
Leonard
Elena
E
Nogales
Tom
T
Vulliamy
Inderjeet S
IS
Dokal
D000741:Anemia, Aplastic; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D019871:Dyskeratosis Congenita / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012042:Registries; D016615:Telomere / Q000378:metabolism; D059506:Telomere Shortening; D034501:Telomere-Binding Proteins / Q000235:genetics*
C544945:Ctc1 protein, human; D034501:Telomere-Binding Proteins