ClinVar

In 4 affected individuals from a large family with telomere-related pulmonary fibrosis and/or bone marrow failure syndrome-9 (PFBMFT9; 620400), Kannengiesser et al. (2020) identified a heterozygous c.17A-G transition (c.17A-G, NM_018648) in the NOP10 gene, resulting in a tyr6-to-cys (Y6C) substitution at a conserved residue in the small N-terminal globular ribbon domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in 140,000 individuals in the gnomAD database. One unaffected family member also carried the mutation, suggesting incomplete penetrance. Functional studies of the mutation and studies of patient cells were not performed, but molecular modeling demonstrated that the affected residue is in a region in close contact with DKC1 (300126) and likely disrupts stability of the domain and the NOP10 complex. Patients with the mutation showed short telomeres, although 1 noncarrier also had short telomeres, suggesting that epigenetic factors may play a role in telomere length.