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Tarailo-Graovac, Maja
(author)
Identification of a large intronic transposal insertion in SLC17A5 causing sialic acid storage disease.
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-02-10
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Springer Science and Business Media LLC,2017
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/250380
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https://gup.ub.gu.se/publication/250380URI
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https://doi.org/10.1186/s13023-017-0584-6DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Sialic acid storage diseases are neurodegenerative disorders characterized by accumulation of sialic acid in the lysosome. These disorders are caused by mutations in SLC17A5, the gene encoding sialin, a sialic acid transporter located in the lysosomal membrane. The most common form of sialic acid storage disease is the slowly progressive Salla disease, presenting with hypotonia, ataxia, epilepsy, nystagmus and findings of cerebral and cerebellar atrophy. Hypomyelination and corpus callosum hypoplasia are typical as well. We report a 16year-old boy with an atypically mild clinical phenotype of sialic acid storage disease characterized by psychomotor retardation and a mixture of spasticity and rigidity but no ataxia, and only weak features of hypomyelination and thinning of corpus callosum on MRI of the brain.The thiobarbituric acid method showed elevated levels of free sialic acid in urine and fibroblasts, indicating sialic acid storage disease. Initial Sanger sequencing of SLC17A5 coding regions did not show any pathogenic variants, although exon 9 could not be sequenced. Whole exome sequencing followed by RNA and genomic DNA analysis identified a homozygous 6040bp insertion in intron 9 of SLC17A5 corresponding to a long interspersed element-1 retrotransposon (KF425758.1). This insertion adds two splice sites, both resulting in a frameshift which in turn creates a premature stop codon 4bp into intron 9.This study describes a novel pathogenic variant in SLC17A5, namely an intronic transposal insertion, in a patient with mild biochemical and clinical phenotypes. The presence of a small fraction of normal transcript may explain the mild phenotype. This case illustrates the importance of including lysosomal sialic acid storage disease in the differential diagnosis of developmental delay with postnatal onset and hypomyelination, as well as intronic regions in the genetic investigation of inborn errors of metabolism.
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Drögemöller, Britt I
(author)
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Wasserman, Wyeth W
(author)
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Ross, Colin J D
(author)
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van den Ouweland, Ans M W
(author)
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Darin, Niklas,1964Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xdarin
(author)
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Kollberg, Gittan,1963Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xkolgi
(author)
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van Karnebeek, Clara D M
(author)
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Blomqvist, Maria K.,1975Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xbmarq
(author)
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Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för pediatrik
(creator_code:org_t)
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In:Orphanet journal of rare diseases: Springer Science and Business Media LLC12:11750-1172
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