Telomere biology disorder prevalence and phenotypes in adults with familial hematologic and/or pulmonary presentations

Simone Feurstein, Ayodeji Adegunsoye, Danijela Mojsilovic, Rekha Vij, Allison H. West DePersia, Padma Sheila Rajagopal, Afaf Osman, Robert H. Collins, Raymond H. Kim, Steven D. Gore, Peter Greenberg, Lucy A. Godley, Zejuan Li, Daniela Del Gaudio, Hari Prasanna Subramanian, Soma Das, Tom Walsh, Suleyman Gulsuner, Jeremy P. Segal, Aliya N. HusainSandeep Gurbuxani, Mary Claire King, Mary E. Strek, Jane E. Churpek

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Telomere biology disorders (TBDs) present heterogeneously, ranging from infantile bone marrow failure associated with very short telomeres to adult-onset interstitial lung disease (ILD) with normal telomere length. Yield of genetic testing and phenotypic spectra for TBDs caused by the expanding list of telomere genes in adults remain understudied. Thus, we screened adults aged $18 years with a personal and/or family history clustering hematologic disorders and/or ILD enrolled on The University of Chicago Inherited Hematologic Disorders Registry for causative variants in 13 TBD genes. Sixteen (10%) of 153 probands carried causative variants distributed among TERT (n 5 6), TERC (n 5 4), PARN (n 5 5), or RTEL1 (n 5 1), of which 19% were copy number variants. The highest yield (9 of 22 [41%]) was in families with mixed hematologic and ILD presentations, suggesting that ILD in hematology populations and hematologic abnormalities in ILD populations warrant TBD genetic testing. Four (3%) of 117 familial hematologic disorder families without ILD carried TBD variants, making TBD second to only DDX41 in frequency for genetic diagnoses in this population. Phenotypes of 17 carriers with heterozygous PARN variants included 4 (24%) with hematologic abnormalities, 67% with lymphocyte telomere lengths measured by flow cytometry and fluorescence in situ hybridization at or above the 10th percentile, and a high penetrance for ILD. Alternative etiologies for cytopenias and/or ILD such as autoimmune features were noted in multiple TBD families, emphasizing the need to maintain clinical suspicion for a TBD despite the presence of alternative explanations. 10.1182/bloodadvances.2020001721.

Original languageEnglish (US)
Pages (from-to)4883-4886
Number of pages4
JournalBlood Advances
Issue number19
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Hematology


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