{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:27:50Z","timestamp":1766420870078,"version":"3.48.0"},"reference-count":86,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital Cataracts, Facial Dysmorphism, and Neuropathy (CCFDN) syndrome is a rare autosomal recessive disorder predominantly found among Vlax Roma populations, caused by a deep intronic founder variant in the CTDP1 gene. This review synthesizes recent advances in understanding the molecular mechanisms of CTDP1 dysfunction, highlighting its central role in transcriptional regulation, RNA splicing, DNA repair, and genome integrity. The unique splicing defect caused by the founder disease-causing variant in the Roma population results in a multisystem phenotype with early-onset neuropathy, congenital cataracts, and characteristic facial dysmorphism. Beyond its genetic homogeneity, CCFDN displays variable clinical severity and presents diagnostic challenges due to overlapping syndromic features. We discuss the emerging therapeutic landscape, focusing on antisense oligonucleotides, small molecule modulators, gene replacement, and genome or transcriptome editing strategies, while emphasizing the challenges in targeted delivery and efficacy. Ongoing insights into CTDP1\u2019s broader biological functions and population genetics inform new directions for diagnosis, genetic counselling, and the development of effective therapies for this severe yet underrecognized disorder.<\/jats:p>","DOI":"10.3390\/ijms27010034","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:27:16Z","timestamp":1766154436000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The CTDP1 Founder Variant in CCFDN: Insights into Pathogenesis, Phenotypic Spectrum and Therapeutic Approaches"],"prefix":"10.3390","volume":"27","author":[{"given":"Iulia Maria","family":"Sabau","sequence":"first","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Chera","sequence":"additional","affiliation":[{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"},{"name":"Doctoral School, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Gabriel","family":"Ungureanu","sequence":"additional","affiliation":[{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"},{"name":"Institute of Biochemistry of the Romanian Academy, 060031 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mircea","family":"Cretu Stancu","sequence":"additional","affiliation":[{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"},{"name":"Genomics Discipline, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7554-4625","authenticated-orcid":false,"given":"Adela","family":"Chirita-Emandi","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology Genetics Discipline, Center of Genomic Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania"},{"name":"Regional Center of Medical Genetics Timis, Emergency Clinical Hospital for Children \u201cLouis Turcanu\u201d, 300011 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Wood","sequence":"additional","affiliation":[{"name":"Medical Sciences Division, Oxford Harrington Rare Disease Centre, Department of Paediatrics, University of Oxford, Oxford OX3 7TY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Puiu","sequence":"additional","affiliation":[{"name":"Doctoral School, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Octavian","family":"Bucur","sequence":"additional","affiliation":[{"name":"Genomics Research and Development Institute, 020021 Bucharest, Romania"},{"name":"Genomics Discipline, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Viron Molecular Medicine Institute, Boston, MA 02108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. 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