Figure  1.

Haplotype and mutational analysis of the TCF8 2916_2917delTG mutation in family UM:139. a, Based on sequencing of cloned versions of the two alleles present in UM:139, the frameshift mutation (M) sequence trace is shown on the left, and the corresponding reference (R) sequence, NM_030751, is shown on the right. b, Haplotyping over the 8.55-cM PPCD3 region, with the 2916_2917delTG mutation designated M and the reference allele designated R. All relationships of genotyped individuals are correct as depicted, as determined from the previously reported UM:139 genome scans (Moroi et al. 2003; Shimizu et al. 2004). A large number of nonparticipating descendants of members of generation II do not appear in this figure. Open symbols indicate absence of PPCD, filled symbols indicate affected individuals, flags indicate individuals with hernia, and crossed symbols indicate individuals considered to have indeterminate phenotypes, since they do not have PPCD but do have other corneal findings, such as guttae or FECD. c, Traits that did not cosegregate with the mutation include late-onset hearing loss, migraine headaches, lupus, and arthritis. The locus map shows the order of markers and intermarker distances. The germline of II-8 contains three distinct versions of chromosome 10 shown among his progeny: unaffected haplotype without deletion (III-3 and III-17), affected haplotype plus deletion (III-1, III-5, III-7, III-10, III-11, and III-12), and affected haplotype without deletion (III-15 and IV-28). The three possible explanations include back mutation, a double recombination event, and germline mosaicism in individual II-9.