RESUMEN
Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the 'molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.
Asunto(s)
Anomalías Múltiples/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Antígenos de Neoplasias/genética , Cerebelo/anomalías , Anomalías del Ojo/genética , Enfermedades Renales Quísticas/genética , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Retina/anomalías , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/epidemiología , Anomalías Múltiples/fisiopatología , Alelos , Proteínas de Ciclo Celular , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Proteínas del Citoesqueleto , Anomalías del Ojo/diagnóstico por imagen , Anomalías del Ojo/epidemiología , Anomalías del Ojo/fisiopatología , Femenino , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Humanos , Japón/epidemiología , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/epidemiología , Enfermedades Renales Quísticas/fisiopatología , Masculino , Mutación , Omán/epidemiología , Linaje , Retina/diagnóstico por imagen , Retina/fisiopatologíaRESUMEN
Anterior Inferior cerebellar artery infarction misdiagnosed as inner ear disease. OBJECTIVE: The clinical >resentation of anterior inferior cerebellar artery (AICA) infarction may mimic that of inner ear disease. lethodology: This report presents two patients with cerebellar artery infarction initially misdiagnosed with inner ear lisease. ase Report: Both the patients presented with sudden hearing loss and vertigo. The patient in case 1 was initially liagnosed with idiopathic sudden sensorineural hearing loss. The patient in case 2 presented with 17 days of vertigo and iearing loss. Both were correctly diagnosed with AICA infarction after performing magnetic resonance imaging. esults and Conclusions: We differentiated AICA from inner ear disease based on the variability in degree and frequency ange of hearing loss, the duration of vertigo, and the manifestation of nystagmus. Because cases of AICA infarction and nner ear disease may present with si'milar symptoms, a detailed examination including clinical course assessments, aboratory findings, and neurological imaging is essential for appropriate diagnosis and treatment.