Extract
Germline telomere-related gene mutations are associated with familial pulmonary fibrosis and lead to short telomere syndrome [1, 2]. Most of the short telomere syndrome-related genes, such as TERT, TERC, DKC1, TINF2, NHP2 and NOP10, were identified in dyskeratosis congenita patients with early onset mucocutaneous manifestations and/or bone marrow failure [3]. The telomerase complex includes TERT, the TERC RNA and DKC1. NOP10, along with DKC1, NHP2 and GAR1, is essential for TERC stability and telomere maintenance [4]. Homozygous NOP10 mutation (c.100C>T, p.Arg34Trp) has been reported only once in a consanguineous family with autosomic recessive dyskeratosis congenita without pulmonary fibrosis [5]. Moreover, the p.Arg34Trp NOP10 mutation caused telomere shortening in homozygous and heterozygous carriers [5]. Here we provide evidence that a heterozygous NOP10 mutation (c.17A>G,p.Tyr6Cys) identified in a large family co-segregates with adult-onset familial pulmonary fibrosis.
Abstract
We provide first evidence that a heterozygous NOP10 mutation (c.17A>G,p.Tyr6Cys) identified in a large family co-segregates with adult-onset familial PF and predisposes to short telomere syndrome (familial PF, liver, haematological diseases) http://bit.ly/2wvXsUd
Footnotes
Conflict of interest: C. Kannengiesser has nothing to disclose.
Conflict of interest: E.D. Manali reports personal fees and non-financial support from Boehringer Ingelheim and Roche, during the conduct of the study.
Conflict of interest: P. Revy has nothing to disclose.
Conflict of interest: I. Callebaut has nothing to disclose.
Conflict of interest: I. Ba has nothing to disclose.
Conflict of interest: A. Borgel has nothing to disclose.
Conflict of interest: C. Oudin has nothing to disclose.
Conflict of interest: A. Haritou has nothing to disclose.
Conflict of interest: L. Kolilekas has nothing to disclose.
Conflict of interest: K. Malagari has nothing to disclose.
Conflict of interest: R. Borie reports grants and personal fees from Boehringer Ingelheim and Roche, personal fees from Savapharma, outside the submitted work.
Conflict of interest: E. Lainey has nothing to disclose.
Conflict of interest: C. Boileau has nothing to disclose.
Conflict of interest: B. Crestani reports personal fees from AstraZeneca and Sanofi, grants, personal fees and non-financial support from Boehringer Ingelheim and Roche, personal fees and non-financial support from BMS, outside the submitted work.
Conflict of interest: S.A. Papiris reports personal fees and non-financial support from Boehringer Ingelheim and Roche, during the conduct of the study.
Support statement: This work (exome sequencing) was supported by a grant “FPI-SPC” from Université Sorbonne Paris Cité (B. Crestani) and the Chancellerie des Universités de Paris (legs Poix; C. Kannengiesser). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received December 21, 2019.
- Accepted February 10, 2020.
- Copyright ©ERS 2020