Schematic representation of the spectrum of ATRX mutations that have been described in boys with ATR-X syndrome with those found in ATMDS. The ATRX gene (top, with introns not to scale) is aligned with ATRX protein (bottom) to allow comparison of the mutation site with functionally important protein domains such as the ADD (ATRX, DNMT3, DNMT3L) zinc-finger domain (ADD includes a C2-C2 type of zinc finger and the closely located PHD motif), helicase domains, P-box, and Q-box. ATR-X–associated mutations are represented above the ideogram of the ATRX gene, and mutations associated with ATMDS are denoted below. (•) Mutations predicted to cause protein truncation (frameshifts and nonsense mutations) and null mutations. (○) Amino acid changes, including in-frame insertions and deletions. Recurrent mutations in ATR-X syndrome are indicated by a number inside the circle, representing the number of families in whom the mutation has been identified. Circles denote point mutations and extended lines denote the extent of large deletions in 2 pedigrees with ATR-X syndrome. Modified with permission from Steensma et al.⁶