3. No additional serious pathogenic mutations on the
X-chromosomes were detected in I2 by exome sequencing
Since MECP2 duplication in I2 might be on the active
X-chromosome, we hypothesized the presence of an additional more serious
pathogenic mutation on the other X-chromosome that would be responsible
for skewing. As Affymetrix CytoScan HD Array detected no other likely
harmful copy number variations in I2 but not in II2. Then we performed
exome sequencing on DNA for females I2 and II2, we screened the
mutations of genes in the OMIM catalog and found some that existed in I2
but not in II2. There were 12 mutations on the X-chromosomes, including
one nonsense mutation and 11 missense mutations. Only three genes
(NROB1 , DMD, and USP9X ) were involved in diseases,
but there was no evidence to show that the three missense gene mutations
were pathogenic (data not shown).