Figure 1.
Pedigree, haplotype analysis, and mutation analysis of the families in this study.
A: Pedigree and disease-haplotype segregation of family A. Blackened symbols represent affected individuals with an abnormal limb phenotype. White symbols represent individuals with a normal limb phenotype. Circles and squares indicate females and males, respectively. The arrows identify the proband and the disease-haplotype is boxed. B: Pedigree and disease-haplotype segregation of family B. C: HOXD13 missense mutations in the two families.
Figure 2.
Photographs and radiographs of individuals.
Phenotypic spectrum of the two families showing typical SD1-c bilateral 3/4 fingers syndactyly (A, B, H, I and J) and unilateral 3/4 fingers syndactyly (G, M and N); transformative SD1-c bilateral 3/4 finger syndactyly with right fifth finger clinodactyly (K and L); mild SPD, bilateral 3/4 fingers syndactyly with phalanx duplication (E and F) and unilateral 3/4 fingers syndactyly with 4/5 fingers synpolydactyly (O and P). Other phenotypes included isolated unilateral partial webbing of 2/3 toes like SD1-a (D) and isolated unilateral adduction deformity of toes (C).
Table 1.
The clinical spectrum in family A and family B with SD1-c.
Table 2.
Two-point LOD score of chromosome 2q markers at various recombination fractions.
Figure 3.
Schematic presentation of the HOXD13 structure and sequences alignment analysis.
A: Schematic presentation of the HOXD13 structure and annotated mutations identified in families. B: Partial amino acid sequences alignment in homeodomain of HOXD13 among several species. The position of mutated amino acid of our cases is indicated by the black box.
Table 3.
Overview of annotated HOXD13 mutations and clinical observations in family members or sporadic cases.
Figure 4.
Transcriptional activity of wild-type and mutant HOXD13 proteins at the human EPH7A promoter.
The R31Q (p.R306Q), R31G (p.R306G) and I47L (p.I322L) mutants show a significantly diminished stimulation compared with the wild-type control at approximately 62%, 60% and 58% of the wild-type HOXD13, respectively. Bars represent firefly/Renilla luciferase ratios for the different constructs.