Pulmonary fibrosis in dyskeratosis congenita withTINF2gene mutation

Exome Sequencing Identifies Mutant TINF2 in a Family With Pulmonary Fibrosis

“…8,9,11 Pulmonary fi brosis has been reported in two adult cases with classic dyskeratosis congenita and aplastic anemia in association with TINF2 mutations. 14, 21 Th ese examples further underscore the rare nature of the isolated FPF presentation in the family we report here. Th e determinants of disease severity beyond telomere length in TINF2 mutation carriers are not known, but it may be that some mutations are hypomorphic, such as in this case given the adult-onset clinical presentation, or that other genetic modifi ers that are yet to be identifi ed aff ect the severity of the telomere defect.…”

Management of suspected monogenic lung fibrosis in a specialised centre

“…Mutations in DKC1, NAF1 and TINF2 are much rarer (figure 1) [9,23,[28][29][30][31][32][33][34][35]. TERT or TERC mutations may be found in about 1-3% of sporadic IPF cases [28].…”

Pulmonary fibrosis associated withTINF2gene mutation: is somatic reversion required?

“…As highlighted by FUKUHARA et al [1], patients with the TINF2 mutation present with severe haematological symptoms before 10 years of age [4]. As mentioned by FUKUHARA et al [1], the identified mutation is probably not hypomorphic because it is a frame-shift deletion located in the mutational ''hot spot'' described previously. Furthermore, the patient presented with very short telomeres.…”

“…Indeed, the electrophoregram depicted in figure 1b in the study by FUKUHARA et al [1] probably comes from a PCR product sub-cloned into an expression vector [5], and does not ensure that the deletion is at the heterozygous status usually seen in our patients ( fig. 1).…”

“…Furthermore, the patient presented with very short telomeres. The TINF2 mutation was probably inherited from her father because he had abnormal skin pigmentation and aplastic anaemia [1].…”