A persistent variant telomere sequence in a human pedigree.

The telomere sequence, TTAGGG, is conserved across all vertebrates and plays an essential role in suppressing the DNA damage response by binding a set of proteins termed shelterin. Changes in the telomere sequence impair shelterin binding, initiate a DNA damage response, and are toxic to cells. Here we identify a family with a variant in the telomere template sequence of telomerase, the enzyme responsible for telomere elongation, that led to a non-canonical telomere sequence.

Rare surfactant-related variants in familial and sporadic pulmonary fibrosis.

The role of constitutional genetic defects in idiopathic pulmonary fibrosis (IPF) is increasingly appreciated. Monogenic disorders associated with IPF affect two pathways: telomere maintenance, accounting for approximately 10% of all patients with IPF, and surfactant biology, responsible for 1%-3% of cases and often co-occurring with lung cancer. We examined the prevalence of rare variants in five surfactant-related genes, SFTPA1, SFPTA2, SFTPC, ABCA3, and NKX2-1, that were previously linked to lung disease in whole genome sequencing data from 431 patients with IPF.