In other species: dog , domestic cat , rabbit

Categories: Lysosomal storage disease , Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610951 (trait) , 611124 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012588: neuronal ceroid lipofuscinosis 7

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN7; NCL7

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."

Associated gene: