High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.

[Etanercept and chronic infection by HCV and HBV]. / Etanercept e infecci (R)n cr (R)nica por los virus de la hepatitis C y B.

Both psoriasis and chronic infections by HBV and HCV have high prevalence. Thus, it is relatively easy for them to coincide in the same patient. If the psoriasis requires systemic treatment, the dermatologist should consider the hepatic comorbidity when selecting an appropriate treatment. Cyclosporine, in addition to other well-known side effects, is an immunosuppressant that may condition worse evolution of the viral hepatitis. On the other hand, retinoids, psoralens and, above all, methotrexate may worsen the liver function. The anti-TNF-|A biological agents are not hepatotoxic and their theoretical contraindication in this context would be because of their action on the immune response and risk of reactivation of the hepatic infection. However, several studies have demonstrated that neither the viral load nor the hepatic inflammation parameters are generally modified negatively when they are used in hepatitis due to HCV. Their use in this context, with correct monitoring, seems, therefore, very reasonable. On the contrary, in chronic hepatitis B virus, there are cases of worsening, even with fatal outcome in some cases, and the use of these biological agents should be reserved for cases having greater need, and always be associated to antiviral treatment and strict monitoring. The review of the recent literature seems to allow the conclusion that the concomitant use of lamivudine would greatly reduce the risk of viral reactivation and, with this condition, the use of etanercept in some HBV+ patients may also be contemplated.

Etanercept e infección cronica por los virus de la hepatitis C y B / Etanercept and chronic infection by HCV and HBV

Tanto la psoriasis como las infecciones crónicas por los virus de la hepatitis B (VHB) y C (VHC) tienen una alta prevalencia, por tanto la coincidencia en un mismo paciente es relativamente fácil. Si se trata de una psoriasis que requiere tratamiento sistémico el dermatólogo deberá considerar la comorbilidad hepática a la hora de seleccionar un tratamiento adecuado. Ciclosporina, además de otros efectos adversos bien conocidos, es un agente inmunosupresor que puede condicionar una peor evolución de la hepatitis vírica. Por otra parte, los retinoides, psoralenos y, sobre todo, metotrexato pueden empeorar la función hepática. Los agentes biológicos anti-factor de necrosis tumoral alfa (TNF-α) no son hepatotóxicos, y su teórica contraindicación en este contexto vendría dada por su acción sobre la respuesta inmune y el eventual riesgo de reactivación de la infección hepática. Sin embargo, diversos estudios han demostrado que ni la carga viral ni los parámetros de inflamación hepática suelen modificarse negativamente cuando se utilizan en hepatitis por el VHC. Su uso en este contexto, con una correcta monitorización, parece por tanto muy razonable. En cambio, en la hepatitis crónica por el VHB, sí existen casos de agravamiento, incluso con desenlace fatal en alguna ocasión, y el uso de estos agentes biológicos debe reservarse para casos de mayor necesidad, siempre asociados a tratamiento antiviral y monitorización estricta. La revisión de la literatura reciente parece permitir la conclusión de que el uso concomitante de lamivudina reduciría mucho el riesgo de reactivación viral y, con esta condición, puede también contemplarse el uso de etanercept en ciertos pacientes positivos para el VHB (AU)

Both psoriasis and chronic infections by HBV and HCV have high prevalence. Thus, it is relatively easy for them to coincide in the same patient. If the psoriasis requires systemic treatment, the dermatologist should consider the hepatic comorbidity when selecting an appropriate treatment. Cyclosporine, in addition to other well-known side effects, is an immunosuppressant that may condition worse evolution of the viral hepatitis. On the other hand, retinoids, psoralens and, above all, methotrexate may worsen the liver function. The anti- TNF-α biological agents are not hepatotoxic and their theoretical contraindication in this context would be because of their action on the immune response and risk of reactivation of the hepatic infection. However, several studies have demonstrated that neither the viral load nor the hepatic inflammation parameters are generally modified negatively when they are used in hepatitis due to HCV. Their use in this context, with correct monitoring, seems, therefore, very reasonable. On the contrary, in chronic hepatitis B virus, there are cases of worsening, even with fatal outcome in some cases, and the use of these biological agents should be reserved for cases having greater need, and always be associated to antiviral treatment and strict monitoring. The review of the recent literature seems to allow the conclusion that the concomitant use of lamivudine would greatly reduce the risk of viral reactivation and, with this condition, the use of etanercept in some HBV + patients may also be contemplated (AU)