A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G).

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined muscle disorders with a primary or predominant involvement of the pelvic or shoulder girdle musculature. More than 20 genes with autosomal recessive (LGMD2A to LGMD2Q) and autosomal dominant inheritance (LGMD1A to LGMD1H) have been mapped/identified to date. Mutations are known for six among the eight mapped autosomal dominant forms: LGMD1A (myotilin), LGMD1B (lamin A/C), LGMD1C (caveolin-3), LGMD1D (desmin), LGMD1E (DNAJB6), and more recently for LGMD1F (transportin-3). Our group previously mapped the LGMD1G gene at 4q21 in a Caucasian-Brazilian family. We now mapped a Uruguayan family with patients displaying a similar LGMD1G phenotype at the same locus. Whole genome sequencing identified, in both families, mutations in the HNRPDL gene. HNRPDL is a heterogeneous ribonucleoprotein family member, which participates in mRNA biogenesis and metabolism. Functional studies performed in S. cerevisiae showed that the loss of HRP1 (yeast orthologue) had pronounced effects on both protein levels and cell localizations, and yeast proteome revealed dramatic reorganization of proteins involved in RNA-processing pathways. In vivo analysis showed that hnrpdl is important for muscle development in zebrafish, causing a myopathic phenotype when knocked down. The present study presents a novel association between a muscular disorder and a RNA-related gene and reinforces the importance of RNA binding/processing proteins in muscle development and muscle disease. Understanding the role of these proteins in muscle might open new therapeutic approaches for muscular dystrophies.

Eficacia de los antivirales en la parálisis de Bell / Efficacy of antiviral in treatment of Bell’s Palsy

Introducción: la parálisis de Bell es una afección frecuente que presenta en 15% de los casos una recuperación incompleta. En los últimos años se ha acumulado evidencia del posible roldel virus herpes simple tipo 1 en su etiología. Objetivos: comparar la eficacia de valaciclovir y prednisona versus prednisona placebo en laparálisis de Bell. Material y método: se realizó un ensayo prospectivo, randomizado y placebo controlado. Delos 41 pacientes incluidos, 21 fueron tratados con valaciclovir 2 g día durante siete días más prednisona (PV) y 19 con prednisona más placebo (PP) administrados oralmente.Los controles clínicos se realizaron a las 2, 4, 8 y 12 semanas, los pacientes con recuperación incompleta fueron seguidos durante seis meses. La recuperación fue definida comosatisfactoria con un puntaje mayor a 90 usando una escala compuesta de parálisis facial (FGS). Resultados: la evolución de la escala de parálisis facial no mostró diferencias significativasentre ambos grupos. La recuperación a los seis meses fue de 86,4% en el grupo PV y 89,5% en el grupo PP (p=0,86). El tiempo medio de recuperación en días fue 70,2 y 71,1, respectivamente (p=0,88). Conclusiones: nuestros resultados no demuestran un beneficio adicional del valaciclovir en eltratamiento de la parálisis de Bell.De acuerdo con las evidencias actuales, no hay consenso respecto al uso rutinario de antivirales en todos los caso de parálisis de Bell (NCT00561106).

Introduction: Bell’s Palsy is a frequent condition, and 15% of patients affected show incomplete recoveries. Over thepast years, wide evidence has been gathered as to the possible incidence of Herpes simplex virus type 1 in itsetiology. Objectives: to compare the efficacy of valacyclovir and prednisone versus prednisone plus placebo. Of 41 patients included in the study, 21 were treated with valacyclovir, 2g a day for seven days, and prednisone; and 19with prednisone plus placebo, administered orally. Clinical controls were carried out at weeks 2, 4, 8 and12. Patients who had incomplete recoveries were followed studied for six months. Recovery was defined as satisfactory when the score was over 90, using a facial paralysis complex scale (FGS – Facial Grading Scale).Results: no meaningful difference in the evolution of the facial paralysis were found between the two groups. After six months, recovery was 86.4% in the valacyclovir and prednisone group, and 89.5% in the prednisone plus placebo group (p=0,86). Average recovery time was 70.2 and 71.1 days, respectively (p=0,88). Conclusions: our results fail to prove additional benefits of the alacyclovir in the treatment of Bell’s Palsy. According to current evidence available, there is no agreementregarding the antivirals ordinary use in all cases of Bell’s Palsy (NCT00561106).

Introdução: a paralisia de Bell é uma afecção freqüente que em 15% dos casos apresenta recuperação incompleta.Nos últimos anos tem-se observado evidência da participação do vírus herpes simplex tipo 1 em sua etiologia.Objetivos: comparar a eficácia da associação valaciclovir e prednisona versus prednisona placebo na paralisiade Bell. Material e método: foi realizado um estudo prospectivo, randomizado e placebo controlado. Dos 41 pacientesincluídos, 21 foram tratados com valaciclovir 2 g/dia durante sete dias mais prednisona (PV) e 19 com prednisona mais placebo (PP) administrados por via oral. Os controles clínicos foram realizados nas semanas 2,4, 8 e 12; os pacientes com recuperação incompleta foram seguidos durante seis meses. A recuperação foi definida como satisfatória quando apresentavam pontuação superior a 90 usando uma escala composta de paralisia facial(FGS). Resultados: a evolução da escala de paralisia facial não mostrou diferenças significativas entre ambos os grupos. A recuperação aos seis meses foi de 86,4% no grupo PV e 89,5% no grupo PP (p=0,86). O tempo médio derecuperação em dias foi 70,2 e 71,1 ,respectivamente (p=0,88).Conclusões: nossos resultados não mostraram um beneficio adicional do uso do valaciclovir no tratamentoda paralisia de Bell. De acordo com as evidências atuais, não existe consensosobre o uso rotineiro de anti-virais em todos los caso de paralisia de Bell (NCT00561106).