{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:42:51Z","timestamp":1785768171103,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"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>Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and\/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the \u201clamina lucida\u201d. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin \u03b16\u03b24 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient\u2019s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G &gt; A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient\u2019s mother, while it was absent in the father\u2019s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies.<\/jats:p>","DOI":"10.3390\/ijms26157343","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T16:16:10Z","timestamp":1753805770000},"page":"7343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Junctional Epidermolysis Bullosa Caused by a Hemiallelic Nonsense Mutation in LAMA3 Revealed by 18q11.2 Microdeletion"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4253-4361","authenticated-orcid":false,"given":"Matteo","family":"Iacoviello","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilidia","family":"Piglionica","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, University Hospital Consortium Polyclinic of Bari, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8311-5747","authenticated-orcid":false,"given":"Ornella","family":"Tabaku","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Garganese","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, University Hospital Consortium Polyclinic of Bari, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5829-2229","authenticated-orcid":false,"given":"Aurora","family":"De Marco","sequence":"additional","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-6152","authenticated-orcid":false,"given":"Fabio","family":"Cardinale","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Giovanni XXIII Pediatric Hospital, Via G. Amendola 207, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1319-4946","authenticated-orcid":false,"given":"Domenico","family":"Bonamonte","sequence":"additional","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"},{"name":"Section of Dermatology and Venereology, University Hospital Consortium Polyclinic of Bari, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-5532","authenticated-orcid":false,"given":"Nicoletta","family":"Resta","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"},{"name":"Medical Genetics Unit, University Hospital Consortium Polyclinic of Bari, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bonamonte, D., Filoni, A., De Marco, A., Lospalluti, L., Nacchiero, E., Ronghi, V., Colagrande, A., Giudice, G., and Cazzato, G. (2022). Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature. 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