Figure 2

A novel duplication of 27 base pairs in the CYP19A1 gene, was identified in the patient reported here. This duplication is predicted to disrupt a critical α-helix of the aromatase enzyme. a. A schematic diagram of the aromatase gene, comprised of nine coding exons (exons 2-9). The location of the novel duplication identified in our patient in exon 8 is shown. b. Results of Sanger sequencing showing a 27 base pair duplication in exon 8 of the CYP19A1 gene from the patient (chr15 (hg19): g.51507347_51507373dup, NM_031226.2: c.915_941dup; NP_112503.1: p.Ala306_Ser314dup) (visualised in Mutation Surveyor® software (Version 2.51, SoftGenetics LLC, Philadelphia, USA)). c. Crystallographic structure of human wild-type aromatase in complex with the cofactor protoporphyrin IX and the substrate androstenedione. The segment of an α-helix in green shows where the duplication occurs. N- and C-terminuses of the α-helix are in orange and magenta, respectively. The rest of aromatase is shown in blue. Protoporphyrin IX, white, and androstenedione, grey. The crystallographic structure is from reference 1 and visualised in PyMOL (Version 1.5.0.3, Schrödinger, LLC). A three-dimensional image of this is provided in the accompanying Additional file 2. d. A close-up showing the α-helix providing binding sites of protoporphyrin IX (white) and androstenedione (grey).