The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome.
Although MECP2 was initially identified as the causative gene in classic Rett syndrome (RTT), the gene has now been implicated in several phenotypes that extend well beyond the clinically defined disorder. MECP2 mutations have been found in people with various disorders, including neonatal onset encephalopathy, X-linked recessive mental retardation (MRX), classic and atypical RTT, autism, and Angelman syndrome, as well as mildly affected females and normal carrier females. To make matters more complex, in approximately 20% of classic sporadic RTT cases and more than 50% of affected sister pairs, no mutation in MECP2 has been found. X-chromosome inactivation patterns can clearly affect the phenotypic expression in females, while the effect of the type and position of the mutation is more apparent in the broader phenotype than in RTT. Both males and females are at risk, although an excess of paternally derived mutations are found in most cases of classic RTT. Thus, because of the range of disparate phenotypes, the gene may account for a relatively large portion of mental retardation in the population.
Hammer
Sara
S
Departments of Human Genetics, Mental Retardation Research Center, University of California, Los Angeles, 695 Chales Young Drive South, Los Angeles California, USA.
Dorrani
Naghmeh
N
Dragich
Joanna
J
Kudo
Shinichi
S
Schanen
Carolyn
C
D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics*; D014960:X Chromosome
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins