Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism.

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Biology

Background:

• The methyl-CpG-binding protein 2 (MECP2) gene is implicated in Rett syndrome, a disorder with autism-like features.
• Rare MECP2 mutations have been found in individuals with autism spectrum disorders (ASD).
• The potential broader role of MECP2 as a predisposing factor in ASD requires investigation.

Purpose of the Study:

• To investigate the involvement of the MECP2 gene as a predisposing factor in autism spectrum disorders.
• To analyze polymorphic markers within and flanking the MECP2 gene for association with ASD.

Main Methods:

• Analysis of microsatellite and single nucleotide polymorphism (SNP) markers spanning the MECP2 gene.
• Transmission disequilibrium test (TDT) applied to two independent family collections (USA and UK, total 219 families).
• Statistical analysis including Bonferroni correction for multiple comparisons.

Main Results:

• A significant association (P = 0.009) was found between a three-marker SNP haplotype of MECP2 and ASD.
• Association was supported by single markers, including an indel marker in intron 2 (P = 0.001, Bonferroni corrected P = 0.006).
• Evidence suggests population-level functional variants of MECP2 may increase ASD risk.

Conclusions:

• The MECP2 gene is a significant candidate predisposing factor for autism spectrum disorders.
• Specific MECP2 variants may confer an increased risk for developing ASD.
• Further research in independent samples is warranted to confirm these findings.