Supplementary Figure 1: PDE3A conservation and whole-genome sequencing.

(a) Multiple-sequence alignment of the PDE3A peptide sequence near the identified mutations in five different species. The altered residues were in a highly conserved PDE3A domain. (b) Genomic coverage of Complete Genomics (CG) whole-genome sequencing of Turkish family members IV/6, IV/7, V/14 and V/30. A mean coverage of 57.39 ± 0.25× for each of the four samples was reached. (c) The detected insertion and deletion (indel) events compared to genome assembly hg19. (d) The substitution events are summarized. To use the complementary advantage of different genome sequencing platforms, we performed whole-genome sequencing of the same Turkish patient, whose DNA was also sequenced by CG, on the Illumina platform to screen for further small sequence variations, structural variants and the inversion breakpoints, which were found in fibroblasts and LCLs by interphase FISH. Among the more than 3 million SNVs and small indels, we identified the missense mutation in PDE3A that was also detected in CG sequencing. c.1334C>A in exon 4 of PDE3A (NM_000921; p.T445N) affects a highly conserved amino acid and was not observed in 1000 Genomes Project data nor among 5,000 exomes (Exome Variant Server, http://evs.gs.washington.edu/EVS/; accessed July 2013), in Sanger sequencing of all non-affected family members or in 200 unrelated Caucasian controls. (e) Electropherograms of the six different missense mutations in PDE3A that introduced amino acid changes at positions 445, 447 and 449; total number of samples analyzed; AFF, affected individuals; NON, unaffected controls.