CLN6, ceroid-lipofuscinosis neuronal 6, encodes a protein expressed in the brain. Mutations cause Lipofuscinosis, types late-infantile aka type 6,and Kufs Disease (type 4A).
"Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter." - [PMID 21549341] "Kufs Disease, the Major Adult Form of Neuronal Ceroid Lipofuscinosis, Caused by Mutations in CLN6."
Note that 9 mutations primarily at the position of conserved amino acids, not (currently) in dbSNP. They are (using as reference sequence NM_017882.2):
- c.200T>C (p.Leu67Pro), [rs154774633]
- c.308G>A (p.Arg103Gln), ][rs154774634]]
- c.139C>T (p.Leu47Phe), rs154774635
- c.17G>C (p.Arg6Thr)
- c.712T>A; 713T>C (p.Phe238Thr)
- c.446G>A (p.Arg149His)
- c.890delC (p.Pro297LeufsX53)
- c.150C>G (p.Tyr50X)
- c.231C>G (p.Asn77Lys)
Mutations in this gene and others have been found to cause the form of neuronal ceroid lipofuscinoses (NCLs) known as variant late-infantile NCL. However, there is no obvious difference between the distribution or location of mutations within the gene causing adult onset Kufs disease type A and the ones causing variant late-infantile NCL. There may well be modifying mutations affecting the phenotypes observed, in addition to effects on the CLN6 protein that are yet to be understood.
Wheeler et al. (2002) identified 6 different mutations in the CLN6 gene in patients with a variant form of late infantile CLN.
Sharp et al. (2003) identified 8 mutations in the CLN6 gene in patients with CLN6.
Kufs disease was described later. [PMID 21549341]