Genomic structure of the genes in the CMT1A/HNPP region. (A)PMP22. Arrowhead indicates marker D17S918, which contains polymorphic CAG repeats. Distances for each intron are shown at bottom, whereas individual exons are numbered attop. We hypothesized that in rare families with CMT accompanied by anticipation, it may be related to an expanded allele of this triplet repeat. To test this hypothesis, we obtained DNA samples from one such family for which the disease locus mapped to 17p11.2–17p12 by linkage analysis (Kovach et al. 1999). We examined the number of CAG repeat in members of this family, but failed to identify any expansion of the triplet repeats in affected individuals (data not shown). A point mutation in PMP22 was subsequently found to segregate with the disease phenotype in this family (Kovach et al. 1999). (B) HS3ST3B1 and HS3ST3A1. HS3STB1 is located inside the CMT1A/HNPP genomic region, whereas HS3STA1 is 569-kb telomeric to the distal CMT1A–REP. Each exon of the two genes is indicated as a box, and arrows show the direction of the transcription. (C) CDRT1 andNPD008/CGI-148. The horizontal shaded rectangle indicates the proximal CMT1A–REP. An open box shows the single exon ofCDRT1 and solid boxes indicate seven exons ofNPD008/CGI-148 that span 26 kb. (D)TEKT3 contains eight exons (solid boxes) including an untranslated first exon. The putative initiating methionine is in exon II. The exon/intron boundaries from exons III to VI, which were not determined by database analyses, were experimentally confirmed by RT–PCR and sequence analyses using single-stranded testis cDNA as the template DNA. (E) CDRT15 in the 11-kb low-copy repeat unit, LCRA1. Hatched horizontal bars indicate repetitive elements. Pseudogene for KIAA1151 is also shown.
