Genomic coordinate 8:1,753,059
Here I present: “Neuronal Ceroid Lipofuscinoses”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (CLN8) 神經性腦脂質突。icd10=E75.4
INTRODUCTION.
Neuronal ceroid lipofuscinosis is a family of at least eight (8) genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body’s tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem “lipo-“, which is a variation on lipid, and from the term “pigment”, used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.
Neuronal ceroid lipofuscinoses are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment patterns observed most often in CLN8 comprise mixed combinations of ‘granular,’ ‘curvilinear,’ and ‘fingerprint’ profiles.
Neuronal ceroid lipofuscinoses are pediatric neurodegenerative diseases with common clinical features. Of the nine (9) clinical variants (CLN1–CLN9), six (6) have been genetically identified. Most variants manifest cell death and dysregulated sphingolipid metabolism, suggesting the proteins defective in these disorders may interact along one pathway.
Neuronal ceroid lipofuscinoses patient-derived cell lines exhibit cell growth and apoptotic defects that reverse following transfection with the wild-type gene. The membrane-bound proteins CLN3, CLN6, and CLN8 complement each other, as do CLN1 and CLN2 proteins, with respect to growth and apoptosis. The CLN2 protein also corrects growth and apoptosis in CLN3-, CLN6-, and CLN8-deficient cell lines. Neither CLN1-deficient nor CLN2-deficient growth defects are corrected by CLN3, CLN6, and CLN8 proteins. CLN2, CLN3, CLN6, and CLN8 proteins co-immunoprecipitate and co-localize to early and/or recycling endosomes and lipid rafts. Additionally, CLN2p and CLN1p co-immunoprecipitate.
Northern epilepsy syndrome (NE) is a subtype of neuronal ceroid lipofuscinosis. The disease is characterized by seizures in early childhood that progressively get worse until after puberty. Once the onset of seizures occurs, mental degradation is seen. This continues into adulthood, even after seizure frequency has decreased. The cause of the disease is a missense mutation on cytogenetic location 8p23.3.
Northern epilepsy syndrome (NE) is a form of neuronal ceroid lipofuscinosis and is a variant of CLN8. There is evidence that the CLN8 transmembrane ER & ERGIC protein (CLN8) gene is encoded on cytogenetic location 8p23.3 and genomic coordinates 8:1,753,059-1,786,570. The screenshot of the CLN8 gene 33,512 bp (base pairs) of DNA sequence length is shown BELOW. Nine (9) other genes besides CLN8 in the 8p23.3 cytogenetic location are listed BENEATH.
| Coordinate | Symbol | Genomic Name |
| 8:1 | WS2C | Waardenburg syndrome, type 2C |
| 8:406,958 | FBXO25 | F-box only protein 25 |
| 8:489,946 | TDRP | Testis development-related protein |
| 8:737,628 | DLGAP2 | Discs large associated protein 2 |
| 8:1,753,059 | CLN8 | CLN8 transmembrane ER & ERGIC protein |
| 8:1,823,329 | ARHGEF10 | Rho guanine nucleotide exchange factor 10 |
| 8:1,973,677 | KBTBD11 | Kelch repeat & BTB/POZ domain protein 11 |
| 8:2,045,046 | MYOM2 | Myomesin 2 |
| 8:2,935,361 | CSMD1 | Cub and Sushi multiple domains 1 |
| 8:6,300,001 | DIH2 | Diaphragmatic hernia 2 |
