RESUMEN
Aicardi syndrome (AIC) is an uncommon neurodevelopmental disorder affecting almost exclusively females. Chief features include infantile spasms, corpus callosal agenesis, and chorioretinal abnormalities. AIC is a sporadic disorder and hypothesized to be caused by heterozygous mutations in an X-linked gene but up to now without any defined candidate region on the X chromosome. Array based comparative genomic hybridisation (array-CGH) has become the method of choice for the detection of microdeletions and microduplications at high resolution. In this study, for the first time, 18 AIC patients were analyzed with a full coverage X chromosomal BAC arrays at a theoretical resolution of 82 kb. Copy number changes were validated by real-time quantitation (qPCR). No disease associated aberrations were identified. For such conditions as AIC, in which there are no familial cases, additional patients should be studied in order to identify rare cases with submicroscopic abnormalities, and to pursue a positional candidate gene approach.
Asunto(s)
Anomalías Múltiples/genética , Agenesia del Cuerpo Calloso , Coroides/anomalías , Cromosomas Humanos X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Retina/anomalías , Espasmos Infantiles/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Proteínas Contráctiles/genética , Cartilla de ADN/genética , Discapacidades del Desarrollo/genética , Femenino , Filaminas , Dosificación de Gen , Humanos , Lactante , Proteínas de Microfilamentos/genética , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , SíndromeRESUMEN
The MECP2 gene is responsible for 80-85% of typical cases of Rett syndrome with deleterious mutations affecting exons 3 and 4. Recently, an alternate transcript including exon 1 was discovered with a new protein isoform (MeCP2_e1) much more abundant in brain. We screened exon 1 of MECP2 for mutations and for large rearrangements in a panel of 212 typical cases of Rett syndrome and one family case with atypical Rett syndrome. We identified two deleterious mutations (c.48_55dup and c.62+2_62+3del) and four large rearrangements encompassing exon 1 of MECP2. We also identified the c.16_21dup alteration formerly reported as c.3_4insGCCGCC and give additional support to classify this sequence variation as polymorphic. In our large panel of typical Rett, mutations affecting exon 1 of MECP2 represent 1% of the deleterious alleles. This study confirms that mutations in exon 1 of MECP2 are a rare cause of Rett syndrome.
