High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: Molecular and clinical findings of Turkish probands |
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Authors: | Mehmet Karaca Burcu Hismi Riza Koksal Ozgul Sefayet Karaca Didem Yucel Yilmaz Turgay Coskun Hatice Serap Sivri Aysegul Tokatli Ali Dursun |
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Affiliation: | 1. Aksaray University, Faculty of Science and Arts, Department of Biology, Aksaray, Turkey;2. Hacettepe University, Faculty of Medicine, Pediatrics Department, Unit of Metabolism, Ankara, Turkey;3. Hacettepe University, Institute of Child Health, Ankara, Turkey;4. Aksaray University, School of Health Science, Aksaray, Turkey |
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Abstract: | Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta-synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype–phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829−2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n = 12, 46.2% neurological presentation), followed by thromboembolic events (n = 6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n = 5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%. |
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Keywords: | AdoMet, S-adenosyl-l-methionine AT, right atrial thrombosis CBS, cystathionine beta-synthase CVST, cerebral venous sinus thrombosis dHPLC, denaturating high-performance liquid chromatography DVT, deep vein thrombosis F, female Hcy, homocysteine KS, kyphoscoliosis LE, lens ectopia LTS, left transverse sinus M, male MA, megaloblastic anemia MF, marfanoid features MR, malar rash MTHFR, methylenetetrahydrofolate reductase MTR, methionine synthase MTRR, methionine synthase reductase MVP, mitral valve prolapse NB, newborn NBS, newborn screening ND, not determined OP, osteopenia PCR, polymerase chain reaction PD, psychomotor delay PLP, pyridoxal 5&prime -phosphate PolyPhen2, polymorphism phenotyping v2 Ri, individual information content RT-PCR, real-time polymerase chain reaction RSS, right sigmoid sinus RTS, right transverse sinus RVT, renal vein thrombosis SERPINE1, serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 SIFT, sorting intolerant from tolerant SSS, superior sagittal sinus |
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