Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease
POMGNT1, encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1, is one of the genes responsible for dystroglycanopathy (DGP), which includes multiple phenotypes such as muscle-eye-brain disease (MEB), congenital muscular dystrophy with intellectual disability, and limb-girdle muscula...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1170089/full |
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| author | Yi-Dan Liu Dan-Dan Tan Dan-Yu Song Yan-Bin Fan Xiao-Na Fu Lin Ge Wei Wei Hui Xiong |
| author_facet | Yi-Dan Liu Dan-Dan Tan Dan-Yu Song Yan-Bin Fan Xiao-Na Fu Lin Ge Wei Wei Hui Xiong |
| author_sort | Yi-Dan Liu |
| collection | DOAJ |
| description | POMGNT1, encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1, is one of the genes responsible for dystroglycanopathy (DGP), which includes multiple phenotypes such as muscle-eye-brain disease (MEB), congenital muscular dystrophy with intellectual disability, and limb-girdle muscular dystrophy Here, we report a case of MEB that is the result of a homozygous variant of POMGNT1 that is revealed through uniparental disomy (UPD). An 8-month-old boy was admitted with mental and motor retardation, hypotonia, esotropia, early onset severe myopia, and structural brain abnormalities. A panel testing of genetic myopathy-related genes was used to identify a homozygous c.636C>T (p.Phe212Phe) variant in exon 7 of POMGNT1 in the patient, a heterozygous c.636C>T variant in the father, and the wild type in the mother. Quantitative polymerase chain reaction (q-PCR) revealed no abnormal copy numbers in exon 7. Trio-based whole-exome sequencing (trio-WES) revealed a possible paternal UPD on chromosome 1 of the patient. Chromosomal microarray analysis (CMA) revealed a 120,451 kb loss of heterozygosity (LOH) on 1p36.33-p11.2, encompassing POMGNT1, and a 99,319 kb loss of heterozygosity on 1q21.2-q44, which indicated UPD. Moreover, RNA sequencing (RNA-seq) verified that the c.636C>T variant was a splice-site variant, leading to skipping of exon 7 (p.Asp179Valfs*23). In conclusion, to the best of our knowledge, we present the first case of MEB caused by UPD, providing valuable insights into the genetic mechanisms underlying this condition. |
| first_indexed | 2024-03-13T07:14:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-13T07:14:56Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5761412c3b924a91bb268dcd88563e212023-06-05T09:31:43ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.11700891170089Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain diseaseYi-Dan Liu0Dan-Dan Tan1Dan-Yu Song2Yan-Bin Fan3Xiao-Na Fu4Lin Ge5Wei Wei6Hui Xiong7Department of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaBeijing Kangso Medical Inspection Co., Ltd., Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaPOMGNT1, encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1, is one of the genes responsible for dystroglycanopathy (DGP), which includes multiple phenotypes such as muscle-eye-brain disease (MEB), congenital muscular dystrophy with intellectual disability, and limb-girdle muscular dystrophy Here, we report a case of MEB that is the result of a homozygous variant of POMGNT1 that is revealed through uniparental disomy (UPD). An 8-month-old boy was admitted with mental and motor retardation, hypotonia, esotropia, early onset severe myopia, and structural brain abnormalities. A panel testing of genetic myopathy-related genes was used to identify a homozygous c.636C>T (p.Phe212Phe) variant in exon 7 of POMGNT1 in the patient, a heterozygous c.636C>T variant in the father, and the wild type in the mother. Quantitative polymerase chain reaction (q-PCR) revealed no abnormal copy numbers in exon 7. Trio-based whole-exome sequencing (trio-WES) revealed a possible paternal UPD on chromosome 1 of the patient. Chromosomal microarray analysis (CMA) revealed a 120,451 kb loss of heterozygosity (LOH) on 1p36.33-p11.2, encompassing POMGNT1, and a 99,319 kb loss of heterozygosity on 1q21.2-q44, which indicated UPD. Moreover, RNA sequencing (RNA-seq) verified that the c.636C>T variant was a splice-site variant, leading to skipping of exon 7 (p.Asp179Valfs*23). In conclusion, to the best of our knowledge, we present the first case of MEB caused by UPD, providing valuable insights into the genetic mechanisms underlying this condition.https://www.frontiersin.org/articles/10.3389/fgene.2023.1170089/fulluniparental disomy (UPD)muscle-eye-brain disease (MEB)PomGnT1dystroglycanopathy (DGP)splice-site variant |
| spellingShingle | Yi-Dan Liu Dan-Dan Tan Dan-Yu Song Yan-Bin Fan Xiao-Na Fu Lin Ge Wei Wei Hui Xiong Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease Frontiers in Genetics uniparental disomy (UPD) muscle-eye-brain disease (MEB) PomGnT1 dystroglycanopathy (DGP) splice-site variant |
| title | Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease |
| title_full | Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease |
| title_fullStr | Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease |
| title_full_unstemmed | Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease |
| title_short | Uniparental disomy for chromosome 1 with POMGNT1 splice-site variant causes muscle-eye-brain disease |
| title_sort | uniparental disomy for chromosome 1 with pomgnt1 splice site variant causes muscle eye brain disease |
| topic | uniparental disomy (UPD) muscle-eye-brain disease (MEB) PomGnT1 dystroglycanopathy (DGP) splice-site variant |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1170089/full |
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