Rett Syndrome

 

RETT SYNDROME

The MECP2 gene is located at Xq28, close to the small pseudoautosomal region 2 (PAR2), at the q-telomere of chromosome X. Disruption of MECP2 in males is usually lethal. Disruption in females can cause RETT syndrome, one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000. RETT syndrome is probably caused by inactivation of the single normal MECP2 copy by DNA-methylation. Female RETT syndrome patients are mosaic for MECP2-expression because X-chromosome inactivation is random.

 

Duplication of the complete MECP2 gene was identified as the cause of severe mental retardation with progressive spasticity in some males (van Esch, H. et al., 2005, Am J Hum Genet.). MECP2 mutations have also been found in patients with a clinical diagnosis of Angelman syndrome. The most common cause of Angelman syndrome can be detected with SALSA® MLPA® probemix ME028 Prader Willi / Angelman.

 

The P015-F1 probemix contains probes for the MECP2, CDKL5, ARX and NTNG1 genes. Defects in these genes are a cause of RETT syndrome and RETT-like syndromes. Furthermore, several probes are present for genes in close proximity to MECP2. One of these probes is located within the pseudoautosomal region 2 (PAR2). In addition, 10 reference probes are included in this probemix, detecting several different autosomal chromosomal locations.

 

The MECP2 gene (4 exons) spans ~75.9 kb of genomic DNA. Start codon is close to the end of exon 2 and stop codon is in exon 4. The 3’ UTR is unusually long: ~8.5 kb. The P015-F1 probemix contains 17 probes for the MECP2 gene, covering each of the four exons. The CDKL5 gene (23 exons) spans ~228 kb of genomic DNA and is located on Xp22.13, ~18.4 Mb from the p-telomere. The P015-F1 probemix contains 4 CDKL5 probes. The ARX gene (5 exons) spans ~12.3 kb of genomic DNA and is located on Xp21.3, ~24.9 Mb from the p-telomere. The P015-F1 probemix contains 2 ARX probes. The NTNG1 gene (6 exons) spans ~341.8 kb of genomic DNA and is located on 1p13, ~107.5 Mb from the p-telomere. The P015-F1 probemix contains 4 NTNG1 probes More probes for the CDKL5, ARX and NTNG1 genes are present in the P189 RETT-like probemix.