Neuronal Intranuclear Inclusion Disease (NOTCH2NLC)
| Dred_ID | RD00040 |
| OMIM ID | 603472 |
| Disease name | Neuronal Intranuclear Inclusion Disease |
| Alternative names | NIID |
| Category | Genetic diseases, Neuronal diseases, Rare diseases, |
| Phenotype | NIH Rare Diseases : Neuronal intranuclear inclusion disease (NIID) is a slowly progressive, neurodegenerative disease. NIID may affect any part of the nervous system (central, peripheral, and/or autonomic), as well as various organs. Signs and symptoms may begin anywhere from infancy to late adulthood, and can vary from person to person. In most cases, the disease begins in childhood. Symptoms of NIID worsen over time and may include dementia, limb weakness, cerebellar ataxia, dystonia, parkinsonism, seizures, and autonomic dysfunction. Therefore, people with NIID may have impairment of balance, movement, cognition, communication, behavior, and the ability to function independently. In general, limb weakness and ataxia are more common in children with NIID, while dementia is more common in people diagnosed in adulthood. The features of NIID result from the presence of eosinophilic intranuclear inclusions inside neurons and glial cells (abnormal masses of substances in the nuclei of cells of the nervous system). The reason this occurs is not known. Both sporadic and familial cases have been reported. However, specific genes known to cause NIID have not yet been found. Currently there is no treatment that cures or slows the progression of NIID, but medications that help control symptoms may improve quality of life. While the disease is ultimately fatal, life expectancy can range significantly, from one year to several decades after the diagnosis. OMIM: OMIM : Neuronal intranuclear inclusion disease (NIID) is characterized pathologically by eosinophilic intranuclear inclusions in neurons of the peripheral, central, and autonomic nervous systems associated with varying degrees of neuronal loss. Symptoms usually begin in childhood but adult-onset cases have also been described. Clinical expression is variable, depending on the sites of maximal neuronal loss, but is usually a multisystem degenerative process of the central nervous system or a visceral neuropathy . |
| Miscellaneouse | Age of onset: All ages (MalaCards) |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | NOTCH2NLC |
| Alias symbols | N2N; NOTCH2NL; NOTCH2NLA |
| Gene name | notch 2 N-terminal like C |
| Gene map locus | 1q21.2; chr1:149,390,621-149,471,833(+) |
| Ensembl Gene ID | ENSG00000264343 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | NOTCH2NLC (Notch 2 N-Terminal Like C) is a Protein Coding gene. An important paralog of this gene is NOTCH2NLA. |
| Repeat unit | CGG |
| Normal repeat copies | 7-60 |
| Pathogenic repeat copies | ≥61 |
| Gene | NOTCH2NLC |
| Repeat location | 5' UTR |
| Chromosome locus | chr1:149390805-149390843 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Abnormal anti-sense transcripts were found from the beginning of or inside the expanded repeat region only in the two affected samples but not in the unaffected samples. |
| Pathway annotation | Reactome, KEGG |
| PMID | 31332381 |
| Authors | Sone J, Mitsuhashi S, Fujita A, Mizuguchi T, Hamanaka K, Mori K, Koike H, Hashiguchi A, Takashima H, Sugiyama H, Kohno Y, Takiyama Y, Maeda K, Doi H, Koyano S, Takeuchi H, Kawamoto M, Kohara N, Ando T, Ieda T, Kita Y, Kokubun N, Tsuboi Y, Katoh K, Kino Y, Katsuno M, Iwasaki Y, Yoshida M, Tanaka F, Suzuki IK, Frith MC, Matsumoto N, Sobue G. |
| Title | Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease |
| Journal | Nature Genetics |
| Year | 2019 |