Fig. 1.

Clinical and genetic findings in four cases of HFS. Pedigrees displaying consanguinity, clinical findings, and Sanger sequencing of the identified ANTXR2 mutations. In each case, the upper sequence panel represents the mutant allele, as compared to reference sequence in a healthy control below. a Clinical features of Case 1 included erythematous plaques, hyperpigmentation, and joint contractures of the lower extremities. Sanger sequencing identified a novel homozygous mutation, c.969del, which is predicted to result in truncated protein product, p.Ile323Metfs*14. b First cousin consanguinity, lower extremity contractures with hyperpigmentation over the medial malleolus, and Sanger sequencing of the c.134C > T (p.Leu45Pro) mutation in Case 2. c Case 3 developed flesh-colored papules on the face, including periauricular lesions, as well as gingival hyperplasia. Sequencing revealed the recurrent mutation c.1073dup (p.Ala359Cysfs*13). d Case 4 presented with characteristic perianal lesions and perioral papules. The same mutation as in Case 3 was identified by Sanger sequencing. The green in Case 3 and 4 represents the amino acid change, p.Ala357Pro, resulting from a common benign polymorphism, c.1069G > C (rs12647691)