Table 1.

Summary of genetic mutations described in telomere biology disorders.

Gene mutation	Product	Inheritance	Disease and phenotype	Frequency	Comment
TERT5–7,17,47,50,54,59	TERT	Autosomal dominant Autosomal recessive	DCa IPFb/FIPc AAd/MDSe Familial Liver Cirrhosis DC HHSf	15–25% 8–15% (familial) 1–3% (sporadic) 3–5% (AA) 20% (familial MDS-AMLi) Rare, unknown Rare	TERT and TERC mutations are the most common TBD mutations and present later in life.
TERC5,6,20,47,50,54,59	Telomerase RNA component	Autosomal dominant	DC IPF/FIP AA/MDS Familial Liver Cirrhosis	10% 8–15% (familial) 1–3% (sporadic) 3–5% (AA) 20% (familial MDS-AML) rare, unknown	TERT and TERC mutations are the most common TBD mutations and present later in life.
DKC110,48	Dyskerin	X-linked recessive	DC HHS IPF/FIP	15–25% rare <1%	Described in severe X-linked DC, which presents in the first decade of life
RTEL119,29,50	RTEL1	Autosomal recessive Autosomal dominant	DC HHS IPF/FIP	Rare Rare 5–10%	–
TINF216,49	TIN2	Autosomal dominant	DC HHS RSg IPF/FIP	Rare Rare Rare <1%	Results in very short telomeres. Presentation ranges from milder disease (e.g., FIP) to early-onset severe diseases (e.g., HHS, DC). Only mutation identified with RS
PARN11,29	PARN	Autosomal dominant Autosomal recessive	IPF/FIP DC HHS	5% Rare Rare	Biallelic and monoallelic variants are associated with DC, HHS, and IPF, respectively
ZCCHC828	ZCCHC8	Autosomal dominant	FIP	Rare	–
NAF1	NAF1	Autosomal dominant	IPF/FIP, CPFEh	<1%	–
NOP1013 NHP218 WRAP5332 CTC112,35	NOP10 NHP2 TCAB1 CTC1	Autosomal recessive	DC	Rare	CTC1 has been described in Coats’ plus
ACD14	TPP1	Autosomal dominant Autosomal recessive	AA DC HHA	Rare Rare	–

References are in numerical superscript.

^aDyskeratosis congenita.

^bIdiopathic pulmonary fibrosis.

^cFamilial interstitial pneumonia.

^dAplastic anaemia.

^eMyelodysplastic syndrome.

^fHoyeraal–Hreidarsson syndrome.

^gRevesz syndrome.

^hCombined pulmonary fibrosis and emphysema.

ⁱAcute myeloid leukaemia-myelodysplastic syndrome.