Molecular characterization of WFS1 in patients with Wolfram syndrome

Item does not contain fulltextWolfram (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome is a rare autosomal-recessive neurodegenerative disorder that is characterized by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing impairment. A gene responsible for Wolfram syndrome (WFS1) has been identified on the short arm of chromosome 4 and subsequently mutations in WFS1 have been described. We have screened 12 patients with Wolfram syndrome from nine Dutch families for mutations in the WFS1-coding region by single-strand conformation polymorphism analysis and direct sequencing. Furthermore, we analyzed the mitochondrial genome for gross abnormalities and the A3243G point mutation in the leucyl-tRNA gene, because Wolfram syndrome shows phenotypic similarities with mitochondrial disease. Seven mutations in WFS1 were identified in six of nine families: two missense mutations, one frameshift mutation, one splice donor site mutation, and three deletions. In addition, a splice variant near the 5'UTR of WFS1 was identified, present in patient as well as control RNA samples in various percentages, alternating the translation initiation consensus sequence. Whether this WFS1 splice variant displays impaired translation efficiency remains to be determined. No MtDNA lesions were identified in any of the Wolfram patients. Our results demonstrate the usefulness of molecular analysis of WFS1 in the refinement of clinical diagnostic criteria for Wolfram syndrome that helps to dissect the clinically overlapping syndromes sharing diabetes mellitus and optic atrophy

Molecular characterization of WFS1 in patients with Wolfram syndrome

Wolfram (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome is a rare autosomal-recessive neurodegenerative disorder that is characterized by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing impairment. A gene responsible for Wolfram syndrome (WTS1) has been identified on the short arm of chromosome 4 and subsequently mutations in WFS1 have been described. We have screened 12 patients with Wolfram syndrome from nine Dutch families for mutations in the WFS1-coding region by single-strand conformation polymorphism analysis and direct sequencing. Furthermore, we analyzed the mitochondrial genome for gross abnormalities and the A3243G point mutation in the leucyl-tRNA gene, because Wolfram syndrome shows phenotypic similarities with mitochondrial disease. Seven mutations in WTS1 were identified in six of nine families: two missense mutations, one frameshift mutation, one splice donor site mutation, and three deletions. in addition, a splice variant near the 5'UTR of WFS1 was identified, present in patient as well as control RNA samples in various percentages, alternating the translation initiation consensus sequence. Whether this WTS1 splice variant displays impaired translation efficiency remains to be deter mined. No MtDNA lesions were identified in any of the Wolfram patients. Our results demonstrate the usefulness of molecular analysis of WFS1 in the refinement of clinical diagnostic criteria for Wolfram syndrome that helps to dissect the clinically overlapping syndromes sharing diabetes mellitus and optic atrophy

Laringocele: uma causa de obstrução de vias aéreas superiores Laryngocele: a cause of upper airway obstruction

Laringoceles são dilatações anormais do sáculo do ventrículo de Morgani da laringe, localizando-se entre a falsa prega vocal e a face interna da cartilagem tireóide. Relevância clínica é rara, sendo o achado de laringoceles assintomáticas em necropsia muito alto. Algumas vezes, pode se apresentar já como uma grande massa cervical, levando à obstrução de vias aéreas e necessitando de intervenção de urgência. Neste trabalho, os autores relatam um caso de laringocele levando à obstrução de vias aéreas superiores, necessitando de traqueostomia de urgência e fazem uma revisão da literatura sobre o tema. Complicações de laringocele incluem infecção (formação de piocele), aspiração de patógenos e subseqüente bronquite e pneumonia, infecção do espaço lateral da faringe (depois de ruptura) e obstrução de vias aéreas superiores, como no caso apresentado. A laringocele, apesar de ser uma doença benigna, é uma causa potencial de obstrução respiratória que pode ameaçar a vida do paciente. O correto diagnóstico e manejo adequado precoce podem evitar que situações de emergência, como a do paciente do caso relatado, levem à morte.<br>Laryngoceles are abnormal dilatations of the laryngeal saccule, which rises between the ventricular folds, the base of the epiglottis and the inner surface of the thyroid cartilage. Clinical symptoms are rare, and the find of asymptomatic laryngoceles in pathology studies are frequent. Sometimes it is presented as cervical swelling causing airway obstruction in need of emergency intervention. In this study, we report a case of upper airway obstruction due to laryngocele treated by emergency tracheotomy and we review of the literature. Laryngocele complications include infection (pyocele formation), pathogens aspirations with subsequent bronchitis and pneumonia and upper airway obstruction, as in the case reported. Despite being benign tumors, laryngoceles cause relevant airway obstruction. Correct diagnosis and proper treatment can preclude emergencies as it happened to our patient hereby reported