Figure 5.

Proposed model for the recombination/repair mechanism originating both duplications in patients T88 and K9228. Illustration of the Xq28 region from 152.45 Mb to 154.65 Mb. The LCRs are represented by differently colored block arrows and genes by red block arrows. The MECP2 duplication is boxed while the additional distal duplication is circled (broken line). (A) Patient T88. Several DSBs occur simultaneously resulting in an excised fragment that is attached through Alu homology, in a direct orientation to the DSB generated proximally from FLNA. Repair of the remaining DSB is performed by BIR in which the BIR fork invaded the DNA duplex of the sister chromatid at a proximal location with microhomology of a few bp, and DNA synthesis proceeded to the telomere. (B) Patient K9228. Similar recombination/repair event in K9228 with minor differences. Several DSBs occur simultaneously resulting in an excised fragment at LCRs DC1649 and DC1650. This fragment is then rejoined, via Alu homology, in an inverted way to the DSB generated at GDI1. Then, the BIR fork invaded the sister chromatid at a more proximal locus, and DNA synthesis continued to the end of the X chromosome.