{"doi":"10.3390/genes15020238","title":"Frameshift Variant in AMPD2 in Cirneco dell’Etna Dogs with Retinopathy and Tremors","abstract":"<jats:p>While the manifestations of many inherited retinal disorders are limited to loss of vision, others are part of a syndrome that affects multiple tissues, particularly the nervous system. Most syndromic retinal disorders are thought to be recessively inherited. Two dogs out of a litter of Cirneco dell′ Etna dogs, both males, showed signs of retinal degeneration, along with tremors and signs described as either atypical seizures or paroxysmal dyskinesias, while the other two male littermates were normal. We named this oculo-neurological syndrome CONS (Cirneco oculo-neurological syndrome), and undertook homozygosity mapping and whole-genome sequencing to determine its potential genetic etiology. Notably, we detected a 1-bp deletion in chromosome 6 that was predicted to cause a frameshift and premature stop codon within the canine AMPD2 gene, which encodes adenosine monophosphate deaminase, an enzyme that converts adenosine 5′-monophosphate (AMP) to inosine 5’-monophosphate (IMP). Genotyping of the available Cirneco population suggested perfect segregation between cases and controls for the variant. Moreover, this variant was absent in canine genomic databases comprised of thousands of unaffected dogs. The AMPD2 genetic variant we identified in dogs presents with retinal manifestations, adding to the spectrum of neurological manifestations associated with AMPD2 variants in humans.</jats:p>","journal":"Genes","year":2024,"id":645477,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":1,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367660,"name":"Jessica K. 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We named this oculo-neurological syndrome CONS (Cirneco oculo-neurological syndrome), and undertook homozygosity mapping and whole-genome sequencing to determine its potential genetic etiology. Notably, we detected a 1-bp deletion in chromosome 6 that was predicted to cause a frameshift and premature stop codon within the canine AMPD2 gene, which encodes adenosine monophosphate deaminase, an enzyme that converts adenosine 5′-monophosphate (AMP) to inosine 5’-monophosphate (IMP). Genotyping of the available Cirneco population suggested perfect segregation between cases and controls for the variant. Moreover, this variant was absent in canine genomic databases comprised of thousands of unaffected dogs. The AMPD2 genetic variant we identified in dogs presents with retinal manifestations, adding to the spectrum of neurological manifestations associated with AMPD2 variants in humans.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":1,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38397227","pmcid":"PMC10887799","openalex_id":"https://openalex.org/W4391814981","authors":[],"funders":[{"funder_name":"Van Sloun Foundation and NEI/NIH","grant_id":"EY-006855","title":null},{"funder_name":"Van Sloun Foundation and NEI/NIH","grant_id":"#RC-CMM-0720-0792-UPA","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY006855","title":null},{"funder_name":"NEI NIH HHS","grant_id":"P30 EY001583","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01EY006855-31","title":"Models for Therapy of Hereditary Retinal Degeneration"}],"total_grants":5,"fwci":0.6462,"citation_percentile":0.63891187,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4425/15/2/238/pdf?version=1707837892","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4425/15/2/238/pdf?version=1707837892","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4425/15/2/238/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/genes15020238","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38397227","host_type":"repository"},{"url":"https://hdl.handle.net/2434/1029402","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10887799","host_type":"repository"},{"url":"https://air.unimi.it/bitstream/2434/1029402/2/genes-15-00238-with-cover.pdf","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10887799/pdf/genes-15-00238.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10887799","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10887799?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/genes15020238","host_type":""},{"url":"https://dx.doi.org/10.3390/genes15020238","host_type":""}],"fields_of_study":["Retinal Development and Disorders","Adenosine and Purinergic Signaling","Cytomegalovirus and herpesvirus research","0303 health sciences","03 medical and health sciences","Animals","Dogs","Male","AMP Deaminase","Frameshift Mutation","Retina","Retinal Degeneration","Tremor","Whole Genome Sequencing"],"mesh_terms":["Whole Genome Sequencing","AMP Deaminase","Animals","Dogs","Humans","Male","Retina","Retinal Degeneration","Tremor","Frameshift Mutation"],"keywords":["Frameshift mutation","Biology","Genetics","Retinal degeneration","Disease gene identification","Retinal","Ataxia","Mutation","Gene","Exome sequencing","Neuroscience","Animal model","Inherited Canine Disease","Oculo-neurological Syndrome","Syndromic Retinal Condition","Male","Whole Genome Sequencing","Article","Retina","AMP Deaminase","Dogs","Tremor","Animals"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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