telomeropathies

Accelerated telomere attrition is the result of mutations in telomere repair genes and genes encoding components of the shelterin complex and related proteins.

Genotype-phenotype correlations show genes responsible for X-linked (DKC1) and severe recessive childhood dyskeratosis congenita, typically with associated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomeropathy in adults, in which multiorgan failure may be prominent.

Telomerase mutations also are etiologic in familial pulmonary fibrosis and cryptic liver disease.

Detection of a telomere disease requires awareness in the clinic, appropriate laboratory testing of telomere content, and genetic sequencing.

In treatment decisions, genetic screening of related donors for hematopoietic stem cell transplantation is critical, and androgen therapy may be helpful.

Telomeres shorten normally with aging, as well as under environmental circumstances, with regenerative stress and oxidative damage.

Telomere biology is complexly related to oncogenesis: telomere attrition is protective by enforcing senescence or apoptosis in cells with a long mitotic history, but telomere loss also can destabilize the genome by chromosome rearrangement and aneuploidy.

Links

 Telomeres at Kimball’s Biology Pages

Open references

 Bone marrow failure and the telomeropathies. Townsley DM, Dumitriu B, Young NS.
Blood. 2014 Oct 30;124(18):2775-83. doi : 10.1182/blood-2014-05-526285 PMID: 25237198 (Free)