{"doi":"10.1002/acn3.52225","title":"Clinical characterization of Collagen <scp>XII</scp>‐related disease caused by biallelic <i>COL12A1</i> variants","abstract":"OBJECTIVE: While there have been several reports of patients with dominantly acting COL12A1 variants, few cases of the more severe recessive Collagen XII-related disorders have previously been documented. METHODS: We present detailed clinical, immunocytochemical, and imaging data on eight additional patients from seven families with biallelic pathogenic variants in COL12A1. RESULTS: All patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging. Five patients presented with a severe congenital phenotype manifesting with profound weakness, significantly delayed or minimal attainment of motor milestones, respiratory insufficiency, and feeding difficulties. Three patients presented with mild-to-moderate muscle weakness and delayed milestones but were able to achieve independent ambulation. Patients were found to have biallelic loss-of-function COL12A1 variants, except for one family (p.I1393Ffs*11/p.A1110D). Consistent with the variable clinical spectrum, in vitro immunocytochemistry analysis in fibroblasts ranged from complete absence of Collagen XII expression in a patient with severe disease, to a mild reduction in a patient with milder disease. INTERPRETATION: Here we characterize the clinical presentation, muscle imaging, and dermal fibroblast immunostaining findings associated with biallelic variants in COL12A1, further establishing COL12A1 as a recessive myopathic Ehlers-Danlos syndrome (mEDS) gene, and expanding the clinical spectrum to include a milder EDS phenotype.","journal":"Annals of Clinical and Translational Neurology","year":2025,"id":538742,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6134,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240285,"name":"Dimah Saade","orcid":"0000-0003-1938-9952","position":1,"is_corresponding":false},{"id":816395,"name":"Pinki Munot","orcid":"0000-0001-9900-798X","position":2,"is_corresponding":false},{"id":1146631,"name":"Chamindra G. 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