What this means
Researchers looked at one family with lung scarring, small head size, and early gray hair. They found a gene break that seems to shorten telomeres, the caps on chromosome ends. This study looked at one family, so it cannot show how common this cause is.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- One family with lung scarring, tested with genetic and telomere methods
- Kind of research
- A study
The science
- Original title
- A Balanced Chromosomal Rearrangement Disrupting the Telomerase RNA Component Gene Causes Short Telomere-Mediated Pulmonary Fibrosis.
- Authors
- Hourvitz N, Neustadter-Blackman M, Unterman A et al.
- Journal
- International journal of molecular sciences
- Published
- Oct 16, 2026
- Study type
- Study · in humans
- PMID
- 42883912 ↗
Abstract
Excessive telomere shortening contributes to pulmonary fibrosis (PF), with at least 30% of familial cases attributed to telomere biology disorders (TBDs). However, TBD-associated PF remains underdiagnosed because of unidentified disease-causing mutations and limited referral for telomere and genetic testing. Here, we combined telomeric restriction fragment analysis, telomere analysis by a long-read Nanopore sequencing method (NanoTelSeq), exome sequencing (ES), and optical genome mapping (OGM) to investigate the underlying cause of disease in a family affected by PF, microcephaly, and premature hair graying. We identified a familial balanced translocation associated with short telomeres, which involved a chromosome 3 breakpoint within the non-coding telomerase RNA component (TERC) gene, disrupting the 451-nucleotide telomerase RNA. Establishing the diagnosis enabled a TBD-tailored protocol and successful lung transplantation in the proband at age 49. These findings identified structural disruption of TERC as a previously unrecognized cause of TBD and broadened the genetic landscape of TBD beyond splicing, single nucleotide substitutions, and insertion/deletion variants. Furthermore, they demonatrate the importance of routine telomere length measurement alongside comprehensive genomic testing in familial PF.
Hourvitz N, Neustadter-Blackman M, Unterman A et al. A Balanced Chromosomal Rearrangement Disrupting the Telomerase RNA Component Gene Causes Short Telomere-Mediated Pulmonary Fibrosis. International journal of molecular sciences. 2026. doi:10.3390/ijms27198667. PMID: 42883912. https://pubmed.ncbi.nlm.nih.gov/42883912/