RESUMEN
Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1. Its product is involved in various cellular processes, including cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA processing and activation of transcription. Spinal muscular atrophy with respiratory distress (SMARD) is clinically and genetically distinct from SMA. Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4). In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus. Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals.
Asunto(s)
Proteínas Portadoras/genética , Proteínas de Unión al ADN , Atrofia Muscular Espinal/genética , Mutación Missense , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Factores de Transcripción , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/química , Cromosomas Humanos Par 11 , Cartilla de ADN , Femenino , Humanos , Recién Nacido , Masculino , Ratones , Datos de Secuencia Molecular , Linaje , Homología de Secuencia de AminoácidoRESUMEN
We describe a case of a three year old unvaccinated child who developed a fulminant diphtheric myocarditis and nephritis four days after the onset of a tonsillar diphtheria. Despite of the administration of antitoxin on day three and four the child died within 48 hours from the beginning of rhythm disturbances. The cardiac involvement rapidly progressed from bradyarrhythmias with the necessity of a temporary pacemaker to ventricular rhythm disturbances with cardiac failure and final ventricular fibrillation.