An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation

Background The clinical spectrum of Rett syndrome (RTT; Mendelian Inheritance in Man [MIM] #312750) in males is considered to be wider than previously expected. Therefore, the existence of RTT with a normal male karyotype is still controversial. Here, we report the first case of a male patient presenting with an early seizure type of Rett-like phenotypes with a missense variant of MECP2. Method An 8-month-old male was admitted to the pediatric department due to an initial seizure event following aspiration pneumonia and was referred to our clinic for the evaluation of unexplained neuroregression. Genomic DNA was prepared from venous blood by standard procedures and was processed at the Yale Center for Genome Analysis (YCGA) for whole exome sequencing (WES). Processing of sequence data, variant calling, and the identification of de novo mutations were then performed. Direct Sanger sequencing was performed following PCR amplification. Result In this patient with a normal karyotype, WES analysis led to the identification of a novel, de novo missense variant of MECP2 (p.Arg133His) that is not observed in the normal population. Conclusion This rare case of an p.Arg133His hemizygous MECP2 missense mutation could guide future treatment and follow-up plans for RETT-like phenotypes.