Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Several monogenic inherited diseases that display features of human premature aging correlate with shortened telomeres, and are referred to collectively as telomeropathies. These disorders have overlapping symptoms and a common underlying mechanism of telomere dysfunction, but also exhibit variable symptoms and age of onset, suggesting they fall along a spectrum of disorders. Primary telomeropathies are caused by defects in the telomere maintenance machinery, whereas secondary telomeropathies have some overlapping symptoms with primary telomeropathies, but are generally caused by mutations in DNA repair proteins that contribute to telomere preservation. Here we review both the primary and secondary telomeropathies, discuss potential mechanisms for tissue specificity and age of onset, and highlight outstanding questions in the field and future directions toward elucidating disease etiology and developing therapeutic strategies.
Keywords: Premature aging; RecQ helicases; Telomerase; Telomere.
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