Identification of Alu elements mediating a partial PMP22 deletion

Neurogenetics. 2006 May;7(2):119-26. doi: 10.1007/s10048-006-0030-8. Epub 2006 Mar 29.

Abstract

Hereditary neuropathy with liability to pressure palsies (HNPP) is most frequently caused by deletion of a 1.4-Mb region in chromosome 17p11.2-12 including the peripheral myelin protein 22 (PMP22) gene. Smaller deletions partially affecting the PMP22 gene are less frequently observed. We identified in a HNPP patient a deletion of the 5' region of PMP22 including non-coding exon 1, coding exons 2 and 3, whereas, exons 4 and 5 were present. PMP22 exon 3- and 4-specific qPCR resulted in a deletion of one exon 3 allele but in the presence of 2 exon 4 alleles. SNP analysis revealed the presence of heterozygosity for PMP22 coding exons 4 and 5. Finally, MLPA specific for the CMT1A region defined this deletion for the entire 5' region of PMP22 (exons 1, 2 and 3). These partial HNPP deletions may be missed by other techniques, e.g., STR marker analysis. Alu elements have been reported to mediate non-allelic recombination events. Bioinformatic analysis revealed 12 Alu elements flanking in close neighbourhood the estimated 40-kb deletion region as candidates for recombination events. PCR primers were designed to identify a breakpoint-spanning product including the respective Alu elements. PCR-driven identification of a junction fragment was successful with AluJo-AluSq and AluYb9-AluSq specific primer pairs comprising the same intronic region of PMP22. Sequence analysis of these breakpoint-overlapping PCR fragments revealed a 29-bp motif including a chi-like sequence (GCTGG) present both in the AluYb9 and the AluSq element. These data confirm that low-copy repeats (LCRs) mediate non-allelic homologous recombinations (NAHR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements*
  • Base Sequence
  • DNA Mutational Analysis
  • Exons
  • Gene Deletion*
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myelin Proteins / genetics*

Substances

  • Myelin Proteins
  • PMP22 protein, human