Figure 2. Family segregating autosomal-recessive amelogenesis imperfecta. (A) Pedigree of Family 2. Right-shaded symbols indicate carriers of the 21-bp exon 10 ENAM insertion mutation. Left-shaded symbols indicate carriers of the 2-bp exon 10 ENAM insertion mutation. Individuals with either left- or right-shaded symbols have clinically evident localized enamel pitting. Representative examples of enamel pitting in these individuals are illustrated by the arrows in the photograph above or below their corresponding pedigree symbol. Completely shaded individuals are compound heterozygotes for both exon 10 ENAM mutations and have clinically apparent generalized thin hypoplastic AI. In the proband (II-4), the maxillary right incisor is fractured. All teeth are hypoplastic and yellowish, consistent with generalized hypoplastic amelogenesis imperfecta. In the affected sibling (II-1), all teeth show generalized hypoplastic yellow enamel. (B) Panorex radiograph of proband (II-4) illustrating generalized enamel hypoplasia. (C) Lateral cephalometric radiograph of individual II-4, showing anterior open bite. (D,E) Results of molecular analysis of the ENAM gene in this family. In D, the left panel shows the wild-type sequence of a portion of exon 10. The middle panel shows the same part of exon 10 from the proband (II-4), showing the g.12946_12947insAGTCAGTACCAGTACTGTGTC mutation (arrow) that results in the insertion of 7 amino acids (p.V340_M341insSQYQYCV), as shown in the right panel. In E, the left panel again shows the wild-type sequence for a portion of exon 10. The middle panel shows the same part of exon 10 from the proband (II-4), showing the previously described 2-bp insertion (indicated by the arrow; g.13185_13186insAG) that results in a frameshift and premature truncation (p.P422fsX448).