OMIA:001962-9542 : Neuronal ceroid lipofuscinosis, 7 in Macaca fuscata
In other species: dog , domestic cat
Categories: Lysosomal storage disease
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610951 (trait) , 611124 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2018
Cross-species summary: CLN7
Inheritance: McBride et al. (2018): "Pedigree analysis of the affected macaques . . . and unaffected kin . . . suggested an autosomal recessive pattern of disease inheritance."
Mapping: McBride et al. (2018): "Segregation analysis [of variants identified via "Whole exome sequencing of three affected, three obligate carrier and three unaffected, unrelated animals"] identified a single haplotype block of 177 variants located on chromosome 4 as associated with affected status of the 9 individuals sequenced . . . 106,658,369–146,307,114 bp"
Molecular basis: McBride et al. (2018) identified the most likely causal variant as a "single base deletion in CLN7 [MFSD8] in exon 8 (c.769delA; p.Ile257LeufsTer36) [which] is predicted to terminate translation prematurely, resulting in the loss of transmembrane domains 7–12 in the encoded lysosomal transmembrane protein CLN7"
Clinical features: McBride et al. (2018): "Affected macaques display progressive neurological deficits including visual impairment, tremor, incoordination, ataxia and impaired balance."
Pathology: McBride et al. (2018): "Imaging, functional and pathological studies revealed that CLN7-/- macaques have reduced retinal thickness and retinal function early in disease, followed by profound cerebral and cerebellar atrophy that progresses over a five to six-year disease course. Histological analyses showed an accumulation of cerebral, cerebellar and cardiac storage material as well as degeneration of neurons, white matter fragmentation and reactive gliosis throughout the brain of affected animals"
Prevalence: McBride et al. (2018): "screening of the ONPRC [Oregon National Primate Research Center] Japanese macaque colony identified a total of 59 heterozygote CLN7+/− carriers and 189 CLN7+/+ macaques that do not carry the c.769delA variant. Consistent with the CLN7 gene mutation being causative of a fatal disease, no homozygous mutant adult Japanese macaques over six years of age were identified."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CLN7||Macaca fuscata||-||no genomic information (-..-)||CLN7||Ensembl|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1030||Neuronal ceroid lipofuscinosis, 7||CLN7||deletion, small (<=20)||Naturally occurring variant||4||c.769delA||p.(I257Lfs*36)||2018||30048804|
|2018||McBride, J.L., Neuringer, M., Ferguson, B., Kohama, S.G., Tagge, I.J., Zweig, R.C., Renner, L.M., McGill, T.J., Stoddard, J., Peterson, S., Su, W., Sherman, L.S., Domire, J.S., Ducore, R.M., Colgin, L.M., Lewis, A.D. :|
|Discovery of a CLN7 model of Batten disease in non-human primates. Neurobiol Dis 119:65-78, 2018. Pubmed reference: 30048804 . DOI: 10.1016/j.nbd.2018.07.013.|
- Created by Frank Nicholas on 15 Feb 2019
- Changed by Frank Nicholas on 15 Feb 2019