{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T11:56:58Z","timestamp":1764331018025,"version":"3.41.2"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T00:00:00Z","timestamp":1566864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873724"],"award-info":[{"award-number":["81873724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Uniparental disomy (UPD) leading to autosomal recessive (AR) diseases is rare. We found an unusual homozygous state in two nonconsanguineous families, and only one parent in each family was a heterozygote.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two patients with homozygosity for pathogenic variants were revealed by whole\u2010exome sequencing (WES), further Sanger sequencing found that only one of the parents was a heterozygote. Initial genotype and copy number variations analysis from WES data of probands involving whole chromosomes 1 and 9 containing these two pathogenic variants were performed, genome\u2010wide single\u2010nucleotide polymorphism (SNP) array analysis was used to confirm these results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole\u2010exome sequencing identified a homozygous c.3423_3424delTG mutation in <jats:italic>AGL<\/jats:italic> in patient 1 and a homozygous c.241\u20101G&gt;C mutation in <jats:italic>SURF1<\/jats:italic> in patient 2. Further parental testing found that only the two patients\u2019 healthy fathers were heterozygous. WES\u2010based copy number and genotype analysis found a copy\u2010neutral loss of heterozygosity (LOH) of whole chromosome 1 in patient 1 and of whole chromosomes 9 and 10 in patient 2. Further genome\u2010wide SNP array and family haplotype analyses confirmed whole paternal uniparental isodisomy (UPiD) 1 in patient 1 and paternal UPiD 9 and maternal UPiD 10 in patient 2. Therefore, UPiD caused AR monogenic glycogen storage disease type\u2010III (GSDIII) in patient 1 and Leigh syndrome in patient 2 through non\u2010Mendelian inheritance of two mutant copies of a gene from each patient's father.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our report highlights that a single NGS\u2010based analysis could allow us to find homozygous sequence variants and copy\u2010neutral LOH in such cases. Our report also describes the first case of GSDIII caused by UPiD 1 and Leigh syndrome caused by UPiD 9.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.945","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T13:21:26Z","timestamp":1566912086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Uniparental isodisomy caused autosomal recessive diseases: NGS\u2010based analysis allows the concurrent detection of homogenous variants and copy\u2010neutral loss of heterozygosity"],"prefix":"10.1002","volume":"7","author":[{"given":"Bing","family":"Xiao","sequence":"first","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huili","family":"Liu","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjie","family":"Fan","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2938-0233","authenticated-orcid":false,"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.285"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw695"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.005"},{"key":"e_1_2_6_6_1","first-page":"314","volume-title":"Chromosome abnormalities and genetic counseling","author":"Gardner R. 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