Fig. 3

Consequence of the genetic alteration at the mRNA level determined by cDNA sequencing in the case of Patient 1. The cDNA of Patient 1 was also sequenced showing that the genetic alteration caused the development of a novel splice site. On a the genomic DNA (“gDNA”) of Patient 1 shows the location of the 12-bp-deletion, “TG” insertion (red box) and the place of the novel splice sequence (blue box) in the intronic part. On b the cDNA sequence of the patient presents the shortened exon 11, the intact exon 12, the inserted “TG” (red box) and the 55 bp intronic nucleotides, furthermore the stop codon (TAA, black box) resulted due to the frameshift in the reading frame. Translation of the altered mRNA might produce a truncated protein with 6 altered amino acids (position 627–632: DGWYLG) and a premature STOP codon at position 633 (b and c)