TP63 mutation and DBD structure.

<p>(A) A missense mutation K193E of p63 DBD in the proband with heterozygous A/G at nucleotide 577. (B) Sequence of exon 5 in normal control. (C) Multiple sequence alignment. K193 of human p63, indicated by the arrow, is evolutionarily conserved as shown in four representative species. Start position of each amino acid sequence is labeled. (D) Location of K193 (shown in blue stick) is located on the protein surface and at the loop L2-A in the crystal structure of p63 DBD monomer (shown in green ribbons, subunit D of PDB 3QYM). (E<i>)</i> K193 (shown in blue space-filling models) is located in the dimer-dimer interface of the type II tetramer (subunits C, D, E, and F of PDB 3QYM). Different subunits are shown as ribbon diagrams in different colors. Mutation of K193 will potentially affect the formation of the type II tetramer.</p

Three types of hands/feet manifestations and malformed teeth.

<p>(A) Symmetrical deformities. Patient III-5: absence of 2nd–3rd fingers and 2nd–3rd toes. Hand radiography: absence of 2nd–3rd phalanges and fusions of the 1st–2nd and 3rd–4th metacarpale in both hands. Feet radiography: absence of 2nd–3rd phalanx and osseous fusion of 1st–2nd metatarsal bone. Left panel: spade-shaped central incisor and open bite. (B) Asymmetric deformities. Patient III-7: Syndactyly of 1st–2nd finger, absence of middle finger, syndactyly of 1st–2nd and 3rd–4th toes. Radiography: missing third phalanges and cutaneous syndactyly of 1st–2nd and 3rd–4th toes. Left panel: cone-shaped left maxillary lateral incisor. (C) Patient II-3: Hands or feet were undistinguished from normal controls. (D) Patient III-3: Absent right maxillary lateral incisor and malformed lingual fossa in the left maxillary lateral incisor.</p

The pedigree of the family and clinical feature of the proband.

<p>Upper panel: Filled symbols represent the affected individuals. The proband is indicated by an arrow. Males are represented by squares, females by circles. A slashed circle indicates a deceased subject. The person whose DNA sample is available for sequencing is marked by “*”. For simplicity, spouses and children of normal siblings in generation II and III are not shown. Lower panel: Clinical feature of the proband. (A) Thinning of hair on the scalp and lateral eyebrows, ocular hypertelorism, and cleft lip. (B) Cleft palate. (C) Syndactyly and ectrodactyly of the hands. (D) Radiography of the hands. (E) Malformation of the feet. (F) Radiography of the feet. (G & H) CT scanning and reconstruction of the head and craniofacial bones.</p