Figure 1.

Mutation identification. (A) Pedigree with index case arrowed. Filled symbols, family members affected by renal stone disease or diagnosed with dRTA; slashes, deceased; central filled symbol, obligate carrier. (B) Genomic DNA sequencing in the index case shows heterozygous substitution of T for C at nucleotide 2,840, resulting in the replacement of methionine by threonine at codon 909 (M909T). (C) This finding leads to loss of the restriction site for NlaIII amplification and NlaIII digestion of exon 20 from five family members, and a normal control shows cosegregation of the mutation with disease. (D) Multiple species sequence alignment of the C terminus of AE1 shows that Met⁹⁰⁹ is highly conserved. (E) The M909T alteration results in loss of a class II PDZ ligand and generates a potential class I PDZ ligand motif.