RESUMEN
PurposeJalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation.Patients and MethodsA seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations.ResultsOcular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electro-retinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects.ConclusionWe identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.
Asunto(s)
Amelogénesis Imperfecta/genética , Proteínas de Transporte de Catión/genética , Mutación Puntual , Retinitis Pigmentosa/genética , Adulto , Distrofias de Conos y Bastones , Consanguinidad , Análisis Mutacional de ADN , Electrorretinografía , Femenino , Humanos , Masculino , Nistagmo Patológico/genética , Linaje , Fenotipo , Fotofobia/genética , Reacción en Cadena de la Polimerasa , Trastornos de la Visión/genéticaRESUMEN
BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-A (PDGF-AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF-2 and PDGF-AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RR-MS) and compared these values with control subjects. METHODS: Twenty-three patients with RR-MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann-Whitney U-test and Spearman's rank correlation were used for analysis. P values of <0.05 were considered significant. RESULTS: Age and sex distribution were similar in both groups. Serum values of FGF-2 were higher in relapse phase compared with remission phase, with a trend toward significance (P=0.052). CSF PDGF-AA showed significant negative correlation with disease duration (correlation coefficient=-0.58, P=0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF-AA was observed (mean±SEM 2.78±0.8 in controls vs. 0.55±0.29 in patients with MS≥2 years, P<0.05). CONCLUSION: Our study was the first to show that CSF PDGF-AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.
Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/metabolismo , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To compare the sympathetic skin responses (SSRs) in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), and healthy controls. METHODS: SSR was recorded on both hands and feet in 30 patients and 20 healthy controls. SSR results (latency measurements) were compared in patients with normal or abnormal brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). RESULTS: Twenty-three (76.6%) and sixteen patients (53.3%) with MS had abnormal SSR recordings based on 2-standard deviation (SD) or 3-SD (from the mean of the control group) abnormality criteria, respectively. Sixty-six percent and 40 percent of patients had abnormal (>2SD) SSR in at least one hand and one foot, respectively. Patients with absent SSR had more severe disease and higher Expanded Disability Status Scale (EDSS) scores. Fourteen patients had an EDSS of zero, of whom nine had abnormal SSR and others had at least one abnormal EP study. Patients with abnormal SSR had significantly more abnormal BAEPs and SEPs than patients with normal SSR. SSR latencies were significantly correlated with EDSS and disease duration (P<0.01). All patients had at least one abnormal electrophysiological study. ROC-curve analysis showed that a cut-off score of 7008 ms as the sum of all-4-limb SSR latencies had a 80% sensitivity and 95% specificity for differentiating MS patients from healthy controls. CONCLUSIONS: This study suggests that SSR is a useful tool for assessment of autonomic function and can be complementary to EDSS and other electrophysiological studies in patients with MS and CIS.