Figure 1.

Affected Individuals and Mutations

(A) Family (F) pedigrees of the seven probands (P; red arrows) of this study and DNA sequence electropherograms illustrating mutations (black arrowheads) and their co-segregation with the disease phenotype. Asterisks denote mosaic state of the corresponding mutation in P1, the father of P2 (I-1) and in P5. IUFD: intrauterine fetal death.

(B) Clinical images. Hands and feet of P1 with bilateral postaxial polydactyly and wide sandal gap. The extra digit of the right hand and foot were surgically removed (B1 and B2). Hands of P2 demonstrating brachydactyly and nail dysplasia. Postaxial polydactyly had been previously corrected (B3). Radiograph of the right hand of P2 with carpal bone fusion (arrowhead) and brachydactyly (B4). Hand radiograph of III-3 (F2) showing postaxial polydactyly (arrowhead) (B5). Clinical image of P2 demonstrating short stature with short limbs (B6). Diastema and abnormal teeth in P4 at age 9 years (B7). Orodental features of P1 with diastema and multiple lower lingual frenula (arrowheads) (B8).

(C) Sites of mutations in the catalytic subunit of PKA. In the full-length C-subunit (left), the mutations are black spheres. p.Ser54Leu and p.His88Arg/Asn are near the active site (top right, teal spheres) and p.Gly137Arg and p.Gly235Arg (bottom right) are at a tethering surface that interacts with partner proteins, in this case the PKA inhibitor (PKI) peptide (yellow), whose tethering helix docks onto this site.