{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:01:00Z","timestamp":1791824460067,"version":"4.3.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"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> This study reports the clinical and genetic features of Brown-Vialetto-Van Laere syndrome (BVVL) type 2 in a case of uniparental disomy of chromosome 8 in mainland China and analyzes the genotype-phenotype correlation through a review of the literature of BVVL type 2 cases.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The clinical characteristics, treatment, and follow-up data of the patient were summarized, and the etiology was identified by whole-exome sequencing and gene chip analysis. Correlations between the genotype and phenotype were analyzed by collecting clinical and genetic data of published cases and our patient.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We identified a homozygous mutation in <jats:italic>SLC52A2<\/jats:italic> (NM_001253815.2 c.1255G&amp;gt;A) by trio-WES. Sanger sequencing confirmed that his father was heterozygous and his mother was wild type. Subsequently, paternal uniparental disomy of chromosome 8 [UPD (8)pat] was confirmed by chromosomal microarray analysis.The patient received long-term oral riboflavin treatment (7\u00a0mg\/kg.d) and was followed up for 40\u00a0months by which time the child\u2019s bulbar palsy, ataxia, and motor function had improved. A review of the literature and statistical analysis found that the symptoms of BVVL type 2 appear at the earliest shortly after birth and at the latest at 10\u00a0years of age. The median age of onset was 2.5\u00a0years, but the overall delay in diagnosis was a median of 5.6\u00a0years. The most common symptoms were hearing loss (83.9%), followed by muscle weakness (80.6%), visual impairment (64.5%), and ataxia (61.3%). To date, a total of 32 mutations in the <jats:italic>SLC52A2<\/jats:italic> gene have been reported, with the most common being a missense mutation. Mutations occur throughout the length of the gene apart from at the N-terminus. In patients with missense mutations, homozygous pattern was more likely to present with ataxia as the first symptom (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), while compound heterozygous pattern was more likely to develop respiratory insufficiency during the course of disease (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). Moreover, patients with one missense mutation located in inside the transmembrane domain were more likely to have respiratory insufficiency than those with mutations both inside and outside the domain (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Riboflavin supplementation was an important factor in determining prognosis (<jats:italic>p<\/jats:italic> &amp;lt; 0.001).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We report the first UPD(8)pat with SLC52A2 homozygous pathogenic mutation case in BVVL type 2, which expand the mutation spectrum of gene.<\/jats:p>","DOI":"10.3389\/fgene.2022.977914","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T08:34:20Z","timestamp":1663230860000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["First report of paternal uniparental disomy of chromosome 8 with SLC52A2 mutation in Brown-vialetto-van laere syndrome type 2 and an analysis of genotype-phenotype correlations"],"prefix":"10.3389","volume":"13","author":[{"given":"Siyu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyu","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ijporl.2017.11.014","article-title":"SLC52A2 mutations cause SCABD2 phenotype: A second report","volume":"104","author":"Babanejad","year":"2018","journal-title":"Int. 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