STRs database » NOTCH2NLC locus

Overview of repeats

Neuronal intranuclear inclusion disease (NIID) is a neurological disease inherited in an autosomal dominant manner, although around two thirds of cases have been found to be sporadic (Ishiura et al. (2019); Sone et al. (2016)). It was described by two research groups that GGC repeats in the 5′ UTR of the NOTCH2NLC gene cause the disease (Ishiura et al. (2019); Nakamura et al. (2020)). Ishiura and colleagues found that in 28 patients, the expansion was in the range of 90-180 repeats. In the control group they did not see any expansions and in 182 unaffected individuals, the repeat range was between 7 and 39 repeats (Ishiura et al. (2019)). This was confirmed by another study a year later showing 330-520 bp repeat length (corresponding to 110-173 trinucleotide repeats) in seven NIID patients (Nakamura et al. (2020)).
In addition, expansions in the NOTCH2NLC gene are also suggested to be the genetic cause for the hereditary essential tremor type 6 (ETM6), which was found in 11 families (Sun et al. (2020)). The repeat length in affected individuals from mainland China was determined to be between 60 and 250 repeats, whereas in the control group it was between 4 and 41 repeats (Sun et al. (2020)).

Fukuda et al. (2021) studied four families in which affected offspring carried 93, 117, 162 or 140 repeats, while their asymptomatic fathers carried larger median expansions of 522, 390, 528 or 650 repeats. The fathers' alleles showed hypermethylation, whereas the shorter alleles in affected offspring were associated with demethylation. Tian et al. (2019) reported NIID-associated expansions from 66 repeats, below the 90-repeat minimum observed in the Ishiura cohort.

→ View STRipy's population-wide repeat data for NOTCH2NLC locus