Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609978 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific description: Lorenzo-Betancor et al. (2022) "present a Yellow-crowned parrot pedigree with a severe progressive early onset neurodegenerative phenotype and widespread Lewy body-like pathology."

Molecular basis: Lorenzo-Betancor et al. (2022): "Whole genome sequencing (WGS) of the three offspring and their parents was performed ... . The WGS data were aligned ... to the budgerigar (Melopsittacus undulatus) reference genome ... . Given the recessive inheritance pattern of the disease (both parents were healthy and related to each other with their three offspring affected), all intergenic variants were first removed, and the remaining variants were restricted to those for which both parents were heterozygous, and the three offspring were homozygotes. ... We identified 88 variants genome-wide that remained after filtering ... one was a missense variant that was located in the calcium-dependent secretion activator 2 (CADPS2; JH556570.1:3828757C > G; c.1675G > C; p.V559L) gene. ... The candidate variant identified in the WGS analysis was assessed for co-segregation with disease by Sanger sequencing in all members of the pedigree ...."

Clinical features: Lorenzo-Betancor et al. (2022): "The phenotype of the three parrots included severe ataxia, rigidity, and tremor, while their parents were phenotypically normal. ... Due to their severe impairment, they were all euthanized at age 3 months ..."

Pathology: Lorenzo-Betancor et al. (2022): "The brains of affected parrots exhibited neuronal loss, spongiosis, and widespread Lewy body-like inclusions in many regions including the midbrain, basal ganglia, and neocortex. Proteasome activity was significantly reduced ... "

Associated gene: