The molecular genetics of the telomere biology disorders

Figures & data

Table 1. DC-associated Genes.

Gene (product)	Inheritance	Disease association	Effect of disease-associated mutations
DKC1 (dyskerin)	XLR, inherited or de novo	DC, HHS	Reduce hTR stability and telomerase activity
TERT (TERT)	AD	IPF, LD, AA, MDS, AL, DC	Reduce telomerase activity, processivity, or recruitment
o	AR	DC, HHS	o
TERC (hTR)	AD	IPF, LD, AA, MDS, AL, DC	Reduce telomerase activity
NHP2 (NHP2)	AR	DC	Reduce hTR stability and telomerase activity
NOP10 (NOP10)	AR	DC	Reduce hTR stability and telomerase activity
ACD (TPP1)	AD	AA	Reduce telomerase recruitment to telomeres
o	AR	DC	o
WRAP53 (TCAB1)	AR	DC	Impair telomerase trafficking through Cajal bodies and recruitment to telomeres
TINF2 (TIN2)	AD, mostly de novoAD, ? inherited	DC, HHS, RS, IPF	Multifactorial? Reduce telomere sister cohesion, reduce telomerase recruitment to telomeres, enhance telomere shortening (telomerase-independent)
RTEL1 (RTEL1)	AR	HHS	Impair t-loop stability resulting in t-loop excision
CTC1 (CTC1)	AR	CP, DC	Impair duplex telomere replication
PARN (PARN)	AR	HHS	Alter telomere biology gene transcripts

AD, autosomal dominant; AR, autosomal recessive; XLR, X-linked recessive.

AA, aplastic anemia; CP, Coats' plus; DC, dyskeratosis congenita; HHS, Hoyeraal Hreidarsson syndrome; AL, acute leukemia; IPF, idiopathic pulmonary fibrosis; LD, liver disease; MDS, myelodysplastic syndrome; RS, Revesz syndrome.