WES identifies a novel frameshift mutation in WDR62 . (A) Family pedigree showing the four affected siblings (solid symbols) and unaffected family members (open symbols). Squares represent males, circles females, asterisk denote available DNA. Patient II-1 was selected for WES (black arrow). (B) WES in Patient II-1 revealed a homozygous single-base pair insertion (c.1821dupT) in WDR62 producing a frameshift mutation (p.Arg608Serfs*26). (C) The mutation was validated by Sanger sequencing in all affected siblings (only II-1 and II-2 are shown); parental DNA was unavailable for this study. The mutation is absent in an unaffected control (WT). (D) Reported WDR62 mutations in MCPH2 families. WDR62 is located on chromosome 19q13.12 and contains 32 exons (NM_001083961.1) encoding 1523 amino acids. For clarity, reported WDR62 mutations are annotated as peptide changes (grey). Number sign indicates the compound heterozygous mutation present in one reported family . The homozygous single-base pair insertion identified in the French-Canadian family is also shown (red).