Abstract
Rett syndrome is a neurodevelopmental disorder characterized by regression of motor
and mental abilities in females after a period of normal development. The gene, MECP2, has been reported to be responsible for Rett syndrome. Here, we report the cases
who were at first misdiagnosed as having homozygous mutations, and later corrected
as heterozygous ones. We analyzed the MECP2 gene in three sporadic Japanese patients with Rett syndrome. Direct sequencing by
using a primer set that was originally used in the first report of MECP2 mutation suggested two types of homozygous mutations (R133C and R168X). Previous
reports of these mutations with heterozygous status, as well as the general nature
of dominant inheritance in Rett syndrome females and lethality in hemizygous males,
urged us to confirm the homozygosity of these mutations. By using a newly designed
PCR primer, we found that these mutations actually occurred heterozygously in these
patients. Sequence analyses of PCR products suggested that a C/T polymorphism found
upstream of these mutations caused the preferential PCR amplification of the mutated
alleles. These results recommend paying attention to biased PCR amplification that
may lead to misjudgment of the result for mutational analysis of the MECP2 gene.
Keywords
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References
- Ueber ein eigenartiges hirnatrophisches Syndrom bei Hyperammoniamie in Kindesalter.Wien Med Wochenschr. 1966; 116: 723-738
- Rett syndrome: clinical peculiarities and biological mysteries.Acta Paediatr. 1995; 84: 971-976
- Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl–CpG-binding protein 2.Nat Genet. 1999; 23: 185-188
- Isolation, physical mapping, and Northern analysis of the X-linked human gene encoding methyl CpG-binding protein, MECP2.Mamm Genome. 1996; 7: 533-535
- MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin.Cell. 1997; 88: 471-481
- A complex pattern of evolutionary conservation and alternative polyadenylation within the long 3′-untranslated region of the methyl–CpG-binding protein 2 gene (MECP2) suggests a regulatory role in gene expression.Hum Mol Genet. 1999; 8: 1253-1262
- Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA.Cell. 1992; 69: 905-914
- Dissection of the methyl–CpG binding domain from the chromosomal protein MeCP2.Nucleic Acids Res. 1993; 21: 4886-4892
- Transcriptional repression by the methyl–CpG-binding protein MeCP2 involves a histone deacetylase complex.Nature. 1998; 393: 386-389
- Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.Nat Genet. 1998; 19: 187-191
- Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome.J Hum Genet. 2000; 45: 231-236
- Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots.Am J Hum Genet. 1999; 65: 1520-1529
- Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes.Ann Neurol. 2000; 47: 670-679
- Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.Hum Mol Genet. 2000; 9: 1119-1129
- Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients.Hum Mol Genet. 2000; 9: 1369-1375
- MECP2 mutations account for most cases of typical forms of Rett syndrome.Hum Mol Genet. 2000; 9: 1377-1384
- Preserved speech variant is allelic of classic Rett syndrome.Eur J Hum Genet. 2000; 8: 325-330
Article info
Publication history
Accepted:
September 18,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
