Bone Marrow Failure

Gene: NAF1

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MIM# 620365

Green List (high evidence)

Comment on list classification: Included because of the increased risk for progressive bone marrow failure associated with telomere biology disorders

Created: 4 May 2023, 3:17 a.m. | Last Modified: 4 May 2023, 3:17 a.m.

Panel Version: 1.34

At least 3 probands/families with telomere-related pulmonary fibrosis and a supporting mouse model
PMID: 27510903 - 5 individuals from 2 unrelated families with pulmonary fibrosis-emphysema and extrapulmonary manifestations including myelodysplastic syndrome and liver disease, with LoF variants. Truncated NAF1 was detected in cells derived from patients, and, in cells in which a frameshift mutation was introduced by genome editing telomerase RNA levels were reduced. Shortened telomere length also segregated with the variants. A Naf1+/- mouse model had reduced telomerase RNA levels

ClinVar - 1 nonsense and 2 splice site variants (ID: 2443185, 1338525, 2443184) called LP by the Genetic Services Laboratory, University of Chicago but no clinical details were provided
- SCV002547372.1 - Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center - at least one individual with pulmonary fibrosis and leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted
Sources: Literature

Created: 4 May 2023, 3:12 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148

Publications

• 27510903