Research Paper Volume 7, Issue 11 pp 911—927

A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition


Figure 1. Clinical features and telomere length of the DKC family with the novel T1129P TERT mutation.

(A) Family tree of the consanguineous Libyan family. Family members affected by dyskeratosis congenita (son II-1 (deceased), daughter II-2, son II-4) are indicated in black. Marked in red: patient II-2 who was analyzed in detail in the following figures. (B) Table showing complete blood counts (WBC=white blood cells (n/nl), ANC= absolute neutrophil count (% of WBC), RBC= red blood cells (n/pl), Hb=hemoglobin (g/dl), Plt=platelet count, mean corpuscular volume (MCV in fl) and reticulocytes (**2030** of RBC) and the respective age dependent normal values in brackets of the family members I-1, I-2, II-2, II-3, II-4 and II-5 shown in (A). Family members II-2 and II-4 that were diagnosed with dyskeratosis congenita and were homozygous for the TERTT1129P mutation are highlighted with grey color. Indicated with *: Patient II-2 was on a 3-weekly red cell transfusion regimen and had a red cell transfusion of 15 ml/kg erythrocytes 20 days before the sample was taken; patient II-4 had no history of red blood cell or platelet transfusions. (C) Telomere lengths of the described family determined in lymphocytes and granulocytes of the peripheral blood. Absolute telomere lengths in kb of lymphocytes and granulocytes of the patient II-2, her affected brother II-4, her siblings II-3, II-5 and her parents I-1 and I-2 are shown in the context of age-dependent percentiles (Females: circle, males: square. Parents: light grey, children: black. Marked in red: patient II-2 who was analyzed in detail). The solid lines represent the respective 1%, 50%, 99% percentile curves. The dashed lines represent the 25% and 75% percentile. (D) Schematic representation of the TERT gene with functional domains and known mutations at the C-terminus. Our novel T1129P mutation is depicted in red.