{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:08:06Z","timestamp":1781863686748,"version":"3.54.5"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> Alstr\u00f6m syndrome (AS) is a rare autosomal recessive disorder caused by variants of <jats:italic>ALMS1<\/jats:italic>. The objectives of this study were to describe the clinical and genetic characteristics of 19 Chinese patients with biallelic variants in <jats:italic>ALMS1<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We recruited 19 probands with biallelic disease-causing <jats:italic>ALMS1<\/jats:italic> variants. All patients underwent ophthalmic and systematic evaluations and comprehensive molecular genetic analysis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays were performed to observe the effect of a novel missense variant on <jats:italic>ALMS1<\/jats:italic> pre-mRNA splicing.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We identified 33 causative variants in <jats:italic>ALMS1<\/jats:italic>, including 15 frameshift small indels, 14 non-sense variants, two gross deletions, one splicing variant, and one missense variant. RT-PCR showed that the missense variant c.9542G&amp;gt;A (p.R3181Q) altered pre-mRNA splicing to generate a truncated protein p. (Ser3082Asnfs*6). Retinal dystrophy (RD) was noted in all the patients, followed by metabolism disturbance (obesity or acanthosis nigricans) in 66.7% and hearing impairment in 61.1% of the patients. Patient systemic symptom numbers and their age at evaluation showed a significant positive correlation, and BCVA and age at the last examination showed a moderate correlation. All patients exhibited early-onset RD and severe visual impairment. The exception was one patient carrying homozygous p. R3181Q, who showed a mild visual defect and atypical retinal phenotype.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings expand the pathogenic variant spectrum of <jats:italic>ALMS1<\/jats:italic> and provide the first verification of a novel missense variant caused AS by aberrant pre-mRNA splicing. Patients with AS might demonstrate varied clinical spectra; therefore, genetic analysis is vital for the early and accurate diagnosis of patients with atypical AS.<\/jats:p>","DOI":"10.3389\/fgene.2022.1104420","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T08:19:47Z","timestamp":1672820387000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel missense ALMS1 variant causes aberrant splicing identified in a cohort of patients with Alstr\u00f6m syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Jie","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3109\/13816810.2011.620055","article-title":"Differentiating Alstr\u00f6m from Bardet-Biedl syndrome (BBS) using systematic ciliopathy genes sequencing","volume":"33","author":"Aliferis","year":"2012","journal-title":"Ophthalmic Genet."},{"key":"B59","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1002\/humu.23233","article-title":"Monogenic diabetes syndromes: Locus-specific databases for Alstr\u00f6m, Wolfram, and Thiamine-responsive megaloblastic anemia","volume":"38","author":"Astuti","year":"2017","journal-title":"Hum. 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