Figure 1.

Heterozygous TUBB4B Substitutions Affecting Arg391 Cause LCA with Hearing Deficiency

(A) Pedigrees of families and segregation analysis of the mutations. m1, c.1172G>A (p.Arg391His); m2, c.1171C>T (p.Arg391Cys); +, wild-type allele. P1, P2, and P3 are affected individuals whose fibroblasts were analyzed. The percentage below the genotype of individuals I2 in families 1 and 2 shows the relative abundance of mutant reads in genomic DNA from lymphocytes.

(B) Sanger sequence traces around the mutation are shown below the corresponding pedigree.

(C and D) Representative eye fundus views and audiograms in two individuals with TUBB4B substitutions affecting Arg391. The eldest individual’s funduscopy image displays features of advanced retinitis pigmentosa with a marked reduction in the caliber of retinal vessels, generalized choroid atrophy, marked macular rearrangements, and numerous pigmentary deposits in the periphery. The fundus of the youngest individual displays similar abnormalities, although to a much lesser extent (C). Left and right ear pure-tone audiograms of the two individuals displaying moderate symmetric hearing loss (left and central panels, respectively). Vocal audiograms (right panels) are consistent with pure-tone traces, suggesting that the two individuals have endocochlear deafness (D).