Novel non-identical MECP2 mutations in Rett syndrome family: a rare presentation

Introduction: Rett syndrome (RS), an X-linked neurodevelopmental disorder and the common cause of mental retardation in females, is caused by methyl CpG binding protein 2 (MECP2) gene mutations with a frequency of more than 95% in classical Rett patients. Majority of RS cases are sporadic but few familial cases caused by either skewed X-chromosome inactivation in healthy female carriers or mosaicism in male carriers are also reported. Most of the times, the mutation carried in a family is the same as found in affected child.

Methods and results: Here we report a unique family carrying non-identical MECP2 mutations in exon 2 wherein the proband with classical RS was carrying a de-novo early truncating frameshift mutation while her asymptomatic mother was carrying a missense mutation, both predicted as pathogenic mutations.

Conclusions: These findings further validate the importance of MECP2 mutation screening in parents of all mutation positive patients and careful evaluation of the pathogenicity of the mutation found in asymptomatic carriers before providing genetic counseling to the family. The results also propose the role of other factors including other gene mutations, environmental and epigenetics factors in modifying the expression of MECP2 mutations.