A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination
Abstract Background Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation. De novo variants in the SLC35A2 gene, which encodes a UDP‐galactose transporter, are responsible for CDGs with an X‐linked dominant...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Wiley
2019-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.814 |
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| author | Sachiko Miyamoto Mitsuko Nakashima Tsukasa Ohashi Takuya Hiraide Kenji Kurosawa Toshiyuki Yamamoto Junichi Takanashi Hitoshi Osaka Ken Inoue Takehiro Miyazaki Yoshinao Wada Nobuhiko Okamoto Hirotomo Saitsu |
| author_facet | Sachiko Miyamoto Mitsuko Nakashima Tsukasa Ohashi Takuya Hiraide Kenji Kurosawa Toshiyuki Yamamoto Junichi Takanashi Hitoshi Osaka Ken Inoue Takehiro Miyazaki Yoshinao Wada Nobuhiko Okamoto Hirotomo Saitsu |
| author_sort | Sachiko Miyamoto |
| collection | DOAJ |
| description | Abstract Background Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation. De novo variants in the SLC35A2 gene, which encodes a UDP‐galactose transporter, are responsible for CDGs with an X‐linked dominant manner. Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings. Methods Whole‐exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing. cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes. The X‐chromosome inactivation pattern was studied using the human androgen receptor assay. Results We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures. The variant led to an aberrant splicing resulting in an in‐frame 33‐bp insertion, which caused an 11‐amino acid insertion in the presumptive cytoplasmic loop. X‐inactivation pattern was random. Partial loss of galactose and sialic acid of the N‐linked glycans of serum transferrin was observed. Conclusion This case would expand the phenotypic spectrum of SLC35A2‐related disorders to delayed myelination with spasticity and no seizures. |
| first_indexed | 2024-04-13T13:09:19Z |
| format | Article |
| id | doaj.art-2c42000874a347f7a74bdb1f9386b81e |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-13T13:09:19Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-2c42000874a347f7a74bdb1f9386b81e2022-12-22T02:45:40ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-08-0178n/an/a10.1002/mgg3.814A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelinationSachiko Miyamoto0Mitsuko Nakashima1Tsukasa Ohashi2Takuya Hiraide3Kenji Kurosawa4Toshiyuki Yamamoto5Junichi Takanashi6Hitoshi Osaka7Ken Inoue8Takehiro Miyazaki9Yoshinao Wada10Nobuhiko Okamoto11Hirotomo Saitsu12Department of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Pediatrics Niigata University Medical and Dental Hospital Niigata JapanDepartment of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanDivision of Medical Genetics Kanagawa Children's Medical Center Yokohama JapanTokyo Women's Medical University Institute for Integrated Medical Sciences Tokyo JapanDepartment of Pediatrics and Pediatric Neurology Tokyo Women's Medical University, Yachiyo Medical Center Yachiyo JapanDepartment of Pediatrics Jichi Medical University Tochigi JapanDepartment of Mental Retardation & Birth Defect Research National Institute of NeuroscienceNational Center of Neurology & Psychiatry JapanDepartment of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Molecular Medicine Osaka Women's and Children's Hospital Osaka JapanDepartment of Molecular Medicine Osaka Women's and Children's Hospital Osaka JapanDepartment of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanAbstract Background Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation. De novo variants in the SLC35A2 gene, which encodes a UDP‐galactose transporter, are responsible for CDGs with an X‐linked dominant manner. Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings. Methods Whole‐exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing. cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes. The X‐chromosome inactivation pattern was studied using the human androgen receptor assay. Results We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures. The variant led to an aberrant splicing resulting in an in‐frame 33‐bp insertion, which caused an 11‐amino acid insertion in the presumptive cytoplasmic loop. X‐inactivation pattern was random. Partial loss of galactose and sialic acid of the N‐linked glycans of serum transferrin was observed. Conclusion This case would expand the phenotypic spectrum of SLC35A2‐related disorders to delayed myelination with spasticity and no seizures.https://doi.org/10.1002/mgg3.814congenital disorders of glycosylationdelayed myelinationSLC35A2spastic paraplegiasplice site variant |
| spellingShingle | Sachiko Miyamoto Mitsuko Nakashima Tsukasa Ohashi Takuya Hiraide Kenji Kurosawa Toshiyuki Yamamoto Junichi Takanashi Hitoshi Osaka Ken Inoue Takehiro Miyazaki Yoshinao Wada Nobuhiko Okamoto Hirotomo Saitsu A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination Molecular Genetics & Genomic Medicine congenital disorders of glycosylation delayed myelination SLC35A2 spastic paraplegia splice site variant |
| title | A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination |
| title_full | A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination |
| title_fullStr | A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination |
| title_full_unstemmed | A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination |
| title_short | A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination |
| title_sort | case of de novo splice site variant in slc35a2 showing developmental delays spastic paraplegia and delayed myelination |
| topic | congenital disorders of glycosylation delayed myelination SLC35A2 spastic paraplegia splice site variant |
| url | https://doi.org/10.1002/mgg3.814 |
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