La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt / Next generation sequencing in the diagnosis of Stargardt's disease

Introducción: La enfermedad de Stargardt es la maculopatía más frecuente en la edad infantil y adulta. Presenta un origen genético por afectación principalmente del gen ABCA4 con herencia autosómica recesiva. Se trata de un gen con características especiales por su gran tamaño y comportamiento, mostrando una elevada tasa de mutaciones. La aparición, desarrollo y accesibilidad económica de las técnicas de secuenciación masiva permiten realizar el diagnóstico genético de la enfermedad de Stargardt. Pacientes y métodos: Se presentan 2 casos clínicos diagnosticados genéticamente de enfermedad de Stargardt mediante la realización de un panel de secuenciación masiva de 298 genes. Resultados: Los pacientes presentaban un fenotipo de maculopatía de ojo de buey con ausencia de flecks y las siguientes mutaciones: c.G5882A:p.Gly1961Glu y c.C3056T:p.T1019M para el caso 1; c.G5882A:p.Gly1961Glu y c.287del:p.Asn96Thrfs·19 para el caso 2. Ambos pacientes comparten la mutación c.G588A:2p.Gly1961Glu que explica su fenotipo similar característico. Conclusiones: La secuenciación masiva es especialmente útil en la enfermedad de Stargardt, pues el gen ABCA4 presenta un gran tamaño y elevada heterogeneidad polimórfica, que se traduce en una amplia variabilidad clínica (AU)

Introduction: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. Patients and methods: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. Results: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs·19 for case 2. Conclusions: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations (AU)

Next generation sequencing in the diagnosis of Stargardt's disease. / La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt.

INTRODUCTION: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. PATIENTS AND METHODS: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. RESULTS: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs*19 for case 2. CONCLUSIONS: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations.

[Supposed nylon allergy after cataract surgery]. / Supuesta alergia al nylon tras cirugía de la catarata.

CASE REPORT: We present the case of a patient operated on for extracapsular cataract extraction of both eyes. Three weeks after the first operation (right eye), the patient presented a local inflammatory reaction at the incision site which was characterized by the existence of whitish exudates of different sizes surrounding the nylon suture. At one week of the second operation, the patient presented the same alteration (left eye), although it was observed sooner and had a greater intensity. The allergy skin tests for nylon and other substances were negative, however the local inflammatory reaction disappeared when the nylon suture was removed. DISCUSSION: This type of reaction, which we have observed in several other patients, has been previously described by others authors, although no clearly established cause has been demonstrated. Both toxicity and allergy to nylon have been proposed as the underlying mechanisms. We consider that a type IV hypersensitivity reaction to nylon may be the underlying mechanism of these reactions although toxicity cannot be ruled out.

Supuesta alergia al nylon tras cirugía de la catarata / Supposed nylon allergy after cataract surgery

Caso clínico: Presentamos el caso de un paciente intervenido de cirugía extracapsular de catarata de ambos ojos. Tres semanas después de la primera intervención (OD), presentó una inflamación localizada en la zona adyacente a la sutura y caracterizada por la existencia de unos exudados blanquecinos de diferentes tamaños en torno al hilo de sutura. A la semana de practicar la segunda intervención (OI), presentó la misma alteración, aunque más precoz y de mayor intensidad. Las pruebas alérgicas al nylon y a otras substancias fueron negativas, pero el cuadro se resolvió al retirar el nylon. Discusión: Este tipo de reacción, que hemos observado en otros pacientes ha sido descrito previamente en la literatura sin que se haya podido demostrar su etiología de forma concluyente. Existe controversia en la bibliografía sobre si su mecanismo patogénico se debe a una supuesta toxicidad al nylon o alergia al mismo. Por nuestra parte, pensamos que este tipo de reacciones puede deberse a una etiología alérgica mediada por hipersensibilidad tipo IV, aunque no podemos descartar un mecanismo tóxico. (AU)