Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype.

[3] The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, and myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), but these components do not always occur.

The disease initially can affect the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.

Of the five mutations described by Heiss and colleagues in Nature Genetics,[10] four were single nucleotide polymorphisms all resulting in the change of highly conserved amino acids.

In three of the cases, the specific amino acids affected (phenylalanine, proline, glycine) are found in the same locus in humans as they are in yeast (S. Cerevisiae) and the brown rat (R.

The relevant nature of dyskerin throughout most species is to catalyze the post-transcriptional pseudouridylation of specific uridines found in non-coding RNAs, such as ribosomal RNA (rRNA).

Nonetheless, mutations that directly affect the telomerase RNA components would presumably exist and should also cause premature aging or DKC-like symptoms.

Premature graying, early dental loss, predisposition to skin cancer, as well as shortening of telomere length continue to be characteristic of this disease.

[9] Dyskeratosis congenita is a disorder of poor telomere maintenance[7] mainly due to a number of gene mutations that give rise to abnormal ribosome function, termed ribosomopathy.

Specifically, the disease is related to one or more mutations which directly or indirectly affect the vertebrate telomerase RNA component (TERC).

[16][17] Sufferers of DKC have been shown to have a reduction in TERC levels invariably affecting the normal function of telomerase which maintains these telomeres.

[11] Thus, if telomerase is not able to efficiently affect the DNA in the beginning of life, chromosomal instability becomes a grave possibility in individuals much earlier than would be expected.

[19] Since the disease has a wide variety of symptoms due to involvement of multiple systems of the body, diagnostic testing depends on the clinical findings in each individual patient.

Dyskeratosis Congenita in regards to stem cell transplantation have to be very carefully treated with low intensity radiation/chemo to avoid potentially catastrophic effects of Host versus graft disease and toxicity to other organs affected by short telomeres which makes them very sensitive to any radiation especially the lungs, and liver.

The reprogrammed DKC cells were able to overcome a critical limitation in TERC levels and restored function (telomere maintenance and self-renewal).