Intellectual disability and bleeding diathesis due to deficient CMP-sialic acid transport
| العنوان: | Intellectual disability and bleeding diathesis due to deficient CMP-sialic acid transport |
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| المؤلفون: | Arjan P.M. de Brouwer, Angel Ashikov, Rita Gerardy-Schahn, Samuel Schmidt, Joris H. Robben, Miski Mohamed, Maïlys Guillard, Ron A. Wevers, B. van den Heuvel, Peter M.T. Deen, Eva Morava, Dirk Lefeber |
| المصدر: | Neurology, 81, 7, pp. 681-7 Neurology, 81, 681-7 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Chemical and physical biology [NCMLS 7], medicine.medical_specialty, Glycosylation, Ataxia, Adolescent, Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3], DCN MP - Plasticity and memory, Blotting, Western, DNA Mutational Analysis, Mutant, Mutation, Missense, Biology, Hemorrhagic Disorders, medicine.disease_cause, Polymorphism, Single Nucleotide, Renal disorder Energy and redox metabolism [IGMD 9], Abnormal protein glycosylation, Genomic disorders and inherited multi-system disorders [IGMD 3], Young Adult, Intellectual Disability, Internal medicine, medicine, Humans, Missense mutation, Child, Glycostation disorders [DCN PAC - Perception action and control IGMD 4], DCN NN - Brain networks and neuronal communication, Genetics, Mutation, Mitochondrial medicine Energy and redox metabolism [IGMD 8], Glycostation disorders [IGMD 4], medicine.disease, Disease gene identification, Pedigree, Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory [NCMLS 6], Renal disorder Membrane transport and intracellular motility [IGMD 9], carbohydrates (lipids), Bleeding diathesis, Membrane transport and intracellular motility Renal disorder [NCMLS 5], Endocrinology, Cytidine Monophosphate N-Acetylneuraminic Acid, Nucleotide Transport Proteins, Mutation testing, Female, Neurology (clinical), medicine.symptom |
| الوصف: | Contains fulltext : 119120.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To identify the underlying genetic defect in a patient with intellectual disability, seizures, ataxia, macrothrombocytopenia, renal and cardiac involvement, and abnormal protein glycosylation. METHODS: Genetic studies involved homozygosity mapping by 250K single nucleotide polymorphism array and SLC35A1 sequencing. Functional studies included biochemical assays for N-glycosylation and mucin-type O-glycosylation and SLC35A1-encoded cytidine 5'-monophosphosialic acid (CMP-sialic acid) transport after heterologous expression in yeast. RESULTS: We performed biochemical analysis and found combined N- and O-glycosylation abnormalities and specific reduction in sialylation in this patient. Homozygosity mapping revealed homozygosity for the CMP-sialic acid transporter SLC35A1. Mutation analysis identified a homozygous c.303G>C (p.Gln101His) missense mutation that was heterozygous in both parents. Functional analysis of mutant SLC35A1 showed normal Golgi localization but 50% reduction in transport activity of CMP-sialic acid in vitro. CONCLUSION: We confirm an autosomal recessive, generalized sialylation defect due to mutations in SLC35A1. The primary neurologic presentation consisting of ataxia, intellectual disability, and seizures, in combination with bleeding diathesis and proteinuria, is discriminative from a previous case described with deficient sialic acid transporter. Our study underlines the importance of sialylation for normal CNS development and regular organ function. |
| وصف الملف: | application/pdf |
| تدمد: | 1526-632X 0028-3878 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4bd2210be2243f322d3a0fb594dd4238Test https://doi.org/10.1212/wnl.0b013e3182a08f53Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4bd2210be2243f322d3a0fb594dd4238 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1526632X 00283878 |
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