A novel DKC1 gene mutation c.1177 A>T (p.I393F) in a case of dyskeratosis congenita with severe telomere shortening

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ).…”

“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ). The incidence of the mucocutaneous triad (skin pigmentation, nail dystrophy, and mucosal leukoplakia), bone marrow failure, thrombocytopenia, and telomere shortening in Asia are similar to that of non-Asia ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ).…”

“…The incidence of the mucocutaneous triad (skin pigmentation, nail dystrophy, and mucosal leukoplakia), bone marrow failure, thrombocytopenia, and telomere shortening in Asia are similar to that of non-Asia ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ). However, the DC-Asians are more likely to develop anemia instead of pulmonary fibrosis than non-Asians apart from the mucocutaneous triad ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ). Unfortunately, the patient involved in our study did not present with anemia; the reason could be due to the lower incidence (35.7%) of anemia in Asian DC population.…”

“…Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ). The incidence of the mucocutaneous triad (skin pigmentation, nail dystrophy, and mucosal leukoplakia), bone marrow failure, thrombocytopenia, and telomere shortening in Asia are similar to that of non-Asia ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ). However, the DC-Asians are more likely to develop anemia instead of pulmonary fibrosis than non-Asians apart from the mucocutaneous triad ( Table 3 ; 1 , 3 , 4 , 7 – 12 , 14 , 16 – 24 , 26 , 28 – 35 , 38 – 42 , 45 , 46 ).…”

The C-terminal extension of dyskerin is a dyskeratosis congenita mutational hotspot that modulates interaction with telomerase RNA and subcellular localization

“…Mutations in the SSD (SHQ1-specific domain) of SHQ1 that interacts with the dyskerin CTE have been shown to reduce the SHQ1-dyskerin interaction in vitro and the growth of yeast cells [ 32 , 33 ]. On the other hand, despite molecular docking prediction that the I393F mutation of dyskerin reduces its interaction with SHQ1 [ 35 ], or in vitro assay that showed mutations in the dyskerin PUA domain affects binding to SHQ1 [ 36 ], no biochemical analysis has been conducted to examine how CTE mutations affect the dyskerin-SHQ1 interaction. Nonetheless, the effects of several CTE mutations on telomerase function have been studied.…”