1/3. autistic disorder and chromosomal mosaicism 46,XY[123]/46,XY,del(20)(pter --> p12.2)[10].We report on a 3-year-old boy with a moderate to severe mental retardation, autistic behavior patterns, and myoclonic epilepsy of early childhood. The cytogenetic analysis of blood lymphocytes revealed a deletion of chromosome 20pter --> p12.2 occurring as mosaicism in 8% of the analyzed metaphases: 46,XY[123]/46,XY,del(20)(pter --> p12.2)[10]. The deletion was confirmed by the recently developed multicolor banding approach and additionally by region specific fluorescence in situ hybridization (FISH) probes. To the best of our knowledge, this is the first report on a patient with autistic behavior with terminal 20p deletion mosaicism reported up to present.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/3. Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients.Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare epilepsy syndrome. In 30 to 70% of SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel alpha-subunit gene (SCN1A) have been identified. The majority of patients have truncating mutations that are predicted to be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing or conformation sensitive gel electrophoresis (CSGE), microdeletions, which are also predicted to be loss-of-function alleles, can easily escape detection. We selected 11 SMEI patients with or without additional features who had no SCN1A mutation detectable with sequencing analysis. In addition, none of the patients was heterozygous for any of the SNPs in SCN1A, indicating that they were either homozygous for all SNPs or hemizygous due to a microdeletion of the gene. We subsequently analyzed these patients for the presence of microdeletions in SCN1A using a quantitative PCR method named multiplex amplicon quantification (MAQ), and observed three patients missing one copy of the SCN1A gene. All three microdeletions were confirmed by fluorescence in situ hybridization (FISH). These findings demonstrate that a substantial percentage of SCN1A-mutation-negative SMEI patients with or without additional features carry a chromosomal microdeletion comprising the SCN1A gene and that haploinsufficiency of the SCN1A gene is a cause of SMEI.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/3. Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy.OBJECTIVE: To identify cryptic chromosomal deletions involving SCN1A in patients with severe myoclonic epilepsy of infancy (SMEI). methods: Thirty-nine patients with SMEI and without SCN1A point mutations and their parents were typed with 14 intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and the extent of genomic deletions were determined by fluorescence in situ hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1. Deletion breakpoints were more finely mapped by typing single-nucleotide polymorphisms and microsatellite markers. RESULTS: We identified three patients with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal chromosome in all subjects. One patient had central precocious puberty and palatoschisis. genotype-phenotype correlations suggest that these clinical features are due to genes centromeric to SCN1A. CONCLUSIONS: patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A. Clinical features other than epilepsy could be associated with SMEI as a consequence of deletions in contiguous genes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |