Figure 1.

Variable malformation severity and incomplete penetrance in the two split-hand/split-foot malformation 1 (SHFM1) families. (A) Hands and feet of the family 1 patient with a de novo translocation. The right hand has a deficient central ray (upper left image). The left hand is normal (upper right image). The right foot shows deficiency of the second and third rays, partial syndactyly of toes 4–5, and a large great toe (lower left). The left foot shows syndactyly of toes 1–2, and deficiency of the terminal phalanx of the third toe with anonychia (lower right). (B) Hands and feet of the family 2 patients with the deletion. In the proband, both feet and the right hand are normal. In the left hand, the central ray is deficient, and in the ring finger there is camptodactyly at the proximal interphalangeal joint (left image). The proband's maternal uncle is severely affected, with the exception of his left foot, which is normal. His left hand is similar to that of his affected nephew, with deficiency of the central ray, camptodactyly of the ring finger, and some shortening and stiffness of the second (index) finger. In the right hand the second and third rays are absent and there is fusion/syndactyly of rays 4–5 with a single digit. The right foot is also severely affected, with absence of the second and third rays, and fusion of rays 4–5 with a single digit (right image). The uncle's affected daughter (no images) has deficiency of the central ray of the right hand and right foot, with the left hand and left foot unaffected. The right hand closely resembles the left hands of her father and proband. (C) Family 2 pedigree and the results of junction fragment PCR sequencing of both affected (black shapes) and unaffected (white shapes) family members, showing incomplete penetrance of the mutation. The two individuals in whom we performed exome sequencing are the proband (black arrow) and his affected uncle. After the deletion was identified, a third individual (the first female affected in this family) was diagnosed with suspected split-hand/split-foot malformation on routine antenatal ultrasound. She has missing central rays (third digit) of the right hand and right foot only.