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Table 1 Telomere Biology Disorders (TBD) stratified by genetic etiology, syndrome, and clinical manifestation

From: Size matters in telomere biology disorders ‒ expanding phenotypic spectrum in patients with long or short telomeres

 

Gene / protein or loci

OMIM no

Function related to telomere function

Inheritance

Clinical manifestation

Clinical telomere biology disorder and causative gene

 Short telomeres

CTC1

#612199

3’ G-overhang regulation

AR

Dyskeratosis congenitaa, Coats plus syndromeb

DKC1

#305000

hTR stability

X-linked

Dyskeratosis congenita, Hoyeraal-Hreidarsson syndromec, pulmonary fibrosis

NAF1

*617868

hTR stability

AD

Pulmonary fibrosis, liver disease, myelodysplastic syndrome

NHP2

#613987

hTR stability

AR

Dyskeratosis congenita

NOP10

#224230

hTR stability

AR

Dyskeratosis congenita

PARN

#616,353

hTR maturation and stability

AD, AR

Pulmonary fibrosis (AD), dyskeratosis congenita (AR), Hoyeraal-Hreidarsson syndrome (AR)

RTEL1

#615190

Telomere replication, 3’ G-overhang regulation

AD, AR

Pulmonary fibrosis (AD), aplastic leukemia (AD), liver disease (AD), dyskeratosis congenita (AD), Hoyeraal-Hreidarsson syndrome (AR)

STN1

#617341

3’ G-overhang regulation

AR

Coats plus syndrome

TERC

#127550

Telomerase RNA scaffold, template

AD

Dyskeratosis congenita, aplastic anemia, pulmonary fibrosis, liver disease, myelodysplastic syndrome, acute myeloid leukemia, Hoyeraal-Hreidarsson syndrome

WRAP53 / TCAB1

#613988

Telomerase function

AR

Dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome

ZCCHC8

#618674

hTR stability

AD

Pulmonary fibrosis

 Short and long telomeres

ACD / TPP1

#616553

Telomerase function

AD, AR

Short telomeres: Aplastic leukemia (AD), Hoyeraal-Hreidarsson syndrome (AR)

Long telomeres: linked to melanoma and chronic lymphocytic leukemia

TERT

#614742

Catalytic telomerase subunit, telomere elongation

AD, AR

Short telomeres: Pulmonary fibrosis (AD), aplastic leukemia (AD), liver disease (AD), myelodysplastic syndrome (AD), acute myeloid leukemia (AD), dyskeratosis congenita (AD/AR), Hoyeraal-Hreidarsson syndrome (AR)

Long telomeres: melanoma (AD)

TINF2

#613990

Regulation of telomere length

AD

Short telomeres: Dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, pulmonary fibrosis, Reversz’ syndromed

Long telomeres: melanoma

POT1

*609377

Telomerase activity, 3’ G-overhang regulation

AD, AR

(Primarily a long telomere syndrome, but listed here due to examples of homozygosity and a Coats plus like phenotype)

Short telomeres: Coats plus syndrome (AR)

Long telomeres: melanoma (AD), chronic lymphocytic leukemia (AD)

 Long telomeres

TERF2IP / RAP1

*605061

‒

AD

Long telomeres: melanoma, chronic lymphocytic leukemia

Genes linked to underlying telomere biology disorder

 

GRHL2

*608576

‒

AR

Pathogenic variants cause poikiloderma with neutropenia and have an overlapping phenotype with dyskeratosis congenita but not short telomeres

LIG4

*601837

‒

AR

Pathogenic variants cause poikiloderma with neutropenia and have an overlapping phenotype with dyskeratosis congenita but not short telomeres

USB1

*613276

‒

AR

Pathogenic variants cause poikiloderma with neutropenia and have an overlapping phenotype with dyskeratosis congenita but not short telomeres

Loci linked to altered telomere length through GWAS studies

 

ACYP2, ATM, DCAF4, DCLRE1B, MPHOSPH6, PARP1, RFWD3, SON, TERF1, TERF2, ZNF208/ZNF257/ZNF676

  1. AD:  Autosomal dominant, AR: Autosomal recessive, hTR:  Human telomerase RNA
  2. # number refering to disease/manifestation in OMIM
  3. * number refering to protein function in OMIM
  4. aOral leukoplakia, changes in cutaneous pigmentation, nail dystrophy, pulmonary fibrosis, liver fibrosis, bone marrow suppression, hematologic cancers and squamous cell carcinoma of the head and neck
  5. bRetinal disease, which result in retinal detachment and loss of vision in combination with leukodystrophy, ataxia, convulsions, and intellectual dysfunction. Osteopenia, anemia, and bleeding from the gastrointestinal tract are also seen
  6. cIntrauterine growth retardation, bone marrow suppression, cerebellar hypoplasia, ataxia, microcephaly, malabsorption, and intestinal inflammation
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Hereditary Cancer in Clinical Practice

ISSN: 1897-4287