Background: Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita. TERC and TERT mutations were also found in patients with aplastic anemia. The aim of this work is to analyze the possible involvement of the telomerase complex gene NOLA1, in a population of Italian AA patients.
Procedure: DNA of 108 AA patients and 170 normal controls was amplified by PCR and analyzed by DHPLC. For each abnormal elution profile PCR products was directly sequenced using ABI prism 3100 Genetic Analyzer.
Results: We identified, in two patients and two control, the new c.390A > T variation, which is not reported in GenBank, and leads to p.H28L amino acidic change. Telomere analysis shows that the subjects carrying the change have a telomere length comparable to that of healthy controls thus suggesting that this variation has no effect on telomerase complex activity.
Conclusions: We did not find any clear disruptive mutation in NOLA1 gene. The non-conservative variation identified in our sample has no effect on telomeres length. This result suggests that heterozygous point mutations in NOLA1 gene are not responsible for AA in our patients at least acting via telomere. However, in our experience, molecular analysis of other telomerase complex gene (TERC, TERT) is important for AA patients and family members in order to set up an adequate therapeutic or surveillance program and identify carriers or exclude them as potential bone marrow donors.