No function (updated: Oct. 10, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is predicted to be membranous by TOPCONS.
Total structural coverage: 50%
No model available.
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The reference OMIM entry for this protein is 204300
Ceroid lipofuscinosis, neuronal, 4a, autosomal recessive; cln4a
A number sign (#) is used with this entry because autosomal recessive neuronal ceroid lipofuscinosis-4A (CLN4A) is caused by homozygous or compound heterozygous mutation in the CLN6 gene (606725) on chromosome 15q21-q23. Mutation in the CLN6 gene can also cause earlier onset of neuronal ceroid lipofuscinosis (CLN6; 601780) with ocular involvement.
DESCRIPTION
Adult-onset neuronal ceroid lipofuscinosis, also known as Kufs disease, is a neurodegenerative disorder without retinal involvement. There are 2 overlapping phenotypes: type A, characterized by progressive myoclonic epilepsy, and type B, characterized by dementia and a variety of motor-system signs (summary by Arsov et al., 2011). In general, the neuronal ceroid lipofuscinoses (NCL; CLN) 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 clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The ultrastructural pattern of lipopigment in CLN4 comprises a mixed pattern of 'granular,' 'curvilinear,' and 'fingerprint' profiles. (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (
256730).
NOMENCLATURE
The CLNs were originally classified broadly according to age at onset. CLN4 classically referred to adult-onset CLN, but at least one other form of CLN (CLN1) can also have onset in adulthood (Arsov et al., 2011).
CLINICAL FEATURES
Kufs (1925) reported a case of adult-onset neuronal ceroid lipofuscinosis with onset at age 26 and death at age 38. Fine et al. (1960) found reports of 18 complete histologic descriptions. Chou and Thompson (1970) reported the morphologic changes in a man who was well until age 17 and died at age 32. A sister was said to have died of a similar clinical picture characterized by seizures, intellectual deterioration, lack of motor control, and development of athetoid movements. The parents were well and were related as first cousins, indicating autosomal recessive inheritance. Dom et al. (1979) described 2 brothers with Kufs disease. In both, the first manifestation took the form of generalized epileptic seizures, at ages 30 and 32, followed by a cerebellar syndrome with myoclonic jerks and extrapyramidal symptoms. Postmortem examination of 1 brother showed extensive storage of ceroid lipofuscin as curvilinear bodies in the central nervous system and in hepatocytes, heart muscle, and retina. The surviving younger brother showed lipofuscin accumulation on peroneal muscle biopsy. The eye grounds were normal. Tobo et al. (1984) reported adult-onset CLN in a 49-year-old man and his 51-year-old sister, characterized by episodic stuporous and psychotic states, mental retardation, generalized convulsions, and ichthyosis vulgaris. Postmortem examination of the woman showed excessive accumulation of lipofuscin throughout the central nervous system, particularly in neurons of the thalamus, substantia nigra, inferior olivary nuclei, brainstem motor nuclei, and cerebral cortex. Of 118 cases in the literature that had been reported as Kufs disease, Berkovic et al. (1988) concluded that only 50 cases fulfilled strict clinical and pathologic criteria for the diagnosis. The 68 cases that were excluded had inadequate data, evidence for a storage disease other t ...
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Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 204300 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).