English and Italian researchers have used high-throughput sequencing to examine unresolved cases of Charcot-Marie-Tooth disease (CMT):
- CGG expansions in the NOTCH2NLC and LRP12 genes have previously been reported in the literature in several CMT patients from Asia,
- 560 cases of CMT diagnosed in the United Kingdom and not elucidated at the molecular level were studied using whole-genome sequencing (using a short-read-only approach) as part of the national 100,000 Genomes Programme,
- no CGG trinucleotide expansions were found in the genes of interest (NOTCH2NLC, LRP12, RILPL1, NUTM2B and ABCD3).
- Only one patient of African origin carried an expansion in the GIPC1 gene, but this was slightly below the pathogenicity threshold.
This work highlights the extreme rarity of these cases but does not rule out ethnic bias in recruitment.
