Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis

GGC repeat expansions in the 5' untranslated region (5'UTR) of the Notch Homolog 2 N-terminal-like C gene (NOTCH2NLC) have been reported to be the genetic cause of neuronal intranuclear inclusion disease (NIID). However, whether they exist in other neurodegenerative disorders remains unclear. To determine whether there is a medium-length amplification of NOTCH2NLC in patients with amyotrophic lateral sclerosis (ALS), we screened 476 ALS patients and 210 healthy controls for the presence of a GGC repeat expansion in NOTCH2NLC by using repeat-primed polymerase chain reaction (RP-PCR) and fragment analysis. The repeat number in ALS patients was 16.11 +/- 5.7 (range 7-46), whereas the repeat number in control subjects was 16.19 +/- 3.79 (range 10-29). An intermediate-length GGC repeat expansion was observed in two ALS patients (numbers of repeats: 45, 46; normal repeat number <= 40) but not in the control group. The results suggested that the intermediate NOTCH2NLC GGC repeat expansion was associated with Chinese ALS patients, and further functional studies for intermediate-length variation are required to identify the mechanism.

Automated summary

GGC repeat expansions in the 5'UTR of the NOTCH2NLC gene have been found to cause neuronal intranuclear inclusion disease (NIID), but their presence in other neurodegenerative disorders is unclear. In this study, we investigated the presence of a medium-length amplification of NOTCH2NLC in patients with amyotrophic lateral sclerosis (ALS). We identified intermediate GGC repeat expansions in two ALS patients but not in the control group, suggesting their association with ALS in Chinese patients.