Identification of de novo chromosomal structural abnormalities using whole genome sequencing / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE To assess the value of whole genome sequencing for the identification of de novo structural chromosomal abnormalities. METHODS Whole genome sequencing was utilized to analyze a boy with a peripheral blood karyotype of 46,XY,ins(3)(q21p13p21). The patient manifested with ocular abnormalities including blepharophimosis and ptosis. RESULTS Whole genome sequencing suggested a fragmentation of chromosome 3 (from position 55 473 257 to 78 341 929) has been inserted into between 136 876 730 to 138 643 831, and the breakpoints have occurred in the intergenic region. Meanwhile, there was a deletion between 138 643 831 and 138 694 476. This region contains FOXL2, a pathogenic gene associated with blepharophimosis-ptosis-epicanthus inversus syndrome. CONCLUSION De novo structural chromosomal abnormalities may be caused by novel breakpoints or microdeletion flanking the deletion region. To confirm its pathogenic nature, a mutation needs to be assessed at both genetic and genomic levels, for which whole genome sequencing is a good option.