Figure 1.

Genetic and molecular analysis of the tvrm267 mutation. (A) By Sanger sequence analysis, a single base pair transition mutation was observed from C>T at nucleotide 1825 of the Adamtsl4 gene (GenBank, NM_001301705). This mutation is predicted to replace the glutamine (Gln) codon at amino acid position 609 with an early termination codon (p.Gln609*). (B) Schematic describing the location of the mutation in Adamtsl4^tvrm267 and ADAMTSL4 mutations found in human patients (5–9,21–24). The specific domains of ADAMTSL4 are illustrated. TSR1 is unusually long because of a large insertion present only in ADAMTSL4 and ADAMTSL6. (C) Nonsense-mediated decay is suggested by comparison of quantitative RT–PCR of mutant and WT control lens and RPE Adamtsl4 mRNA. Error bars reflect propagating error as defined in the Materials and Methods section. **P < 0.01 (n = 4).