Pulmonary fibrosis associated with TINF2 gene mutation: is somatic reversion required?
- 1Dept of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan
- 2Division of Hematology, Dept of Internal Medicine, Nippon Medical School, Tokyo, Japan
- Yoshinori Tanino, Dept of Pulmonary Medicine, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima-City 960-1295, Japan. E-mail: ytanino{at}fmu.ac.jp
From the authors:
We would like to thank C. Kannengiesser and co-workers for their interest in our article [1] and for their patient’s information and comments. They showed that their patient with the TINF2 (telomerase repeat binding factor 1-interacting nuclear factor 2) mutation had the heterozygous mutation, which is usually seen in young patients with dyskeratosis congenita. In addition, they suggested that a somatic reversion might have occurred in our case because figure 1b showed that the deletion was not heterozygous despite the late disease onset [1].
Somatic reversion is a possible mechanism, which may explain late disease onset of dyskeratosis congenita with the TINF2 mutation. In fact, Jongmans et al. [2] described dyskeratosis congenita in a patient with somatic reversion. In this patient, the wild-type allele was observed more than the mutated allele in DNA from his peripheral blood cells despite DNA from his lung tissues revealing heterozygous mutation.
In our case, figure 1b showed n871–874 tetranucleotide AGGA deletion in TINF2 gene [1]. However, because the mutation was a deletion mutation, TA cloning was performed for this analysis as described previously [3]. The result of gene mutation analysis by direct sequencing before TA cloning showed that the mutation was heterozygous (fig. 1). Although it may be possible that somatic reversion of the cells in the lungs led to pulmonary fibrosis in our patient, unfortunately we could not analyse DNA from lung tissues because the patient had passed away and no lung tissue had been retained.
More cases are needed to determine the exact mechanism(s) of dyskeratosis congenita by analysing each affected organ/system in detail.
Footnotes
Conflict of interest: None declared.
- Received March 18, 2014.
- Accepted March 18, 2014.
- © ERS 2014