Creatine transporter deficiency: Novel mutations and functional studies
| Autor: | Michal Tzadok, Orly Ardon, Gali Heimer, Rong Mao, Yuval Landau, Lidia V. Gabis, Chen Hoffmann, Yair Anikster, A. Shilon-Hadass, Melinda Procter, Nicola Longo, S. Sada, Bruria Ben-Zeev |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Microcephaly Creatine transporter deficiency Human fibroblasts Case Report Creatine transport SLC6A8 Biology Creatine HELA cells White matter 03 medical and health sciences chemistry.chemical_compound Exon 0302 clinical medicine Endocrinology Internal medicine Genetics medicine Creatine deficiency lcsh:QH301-705.5 Molecular Biology Gene lcsh:R5-920 Creatinine medicine.disease 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) chemistry biology.protein Creatine kinase lcsh:Medicine (General) 030217 neurology & neurosurgery |
| Zdroj: | Molecular Genetics and Metabolism Reports Molecular Genetics and Metabolism Reports, Vol 8, Iss C, Pp 20-23 (2016) |
| ISSN: | 2214-4269 |
| DOI: | 10.1016/j.ymgmr.2016.06.005 |
| Popis: | X-linked cerebral creatine deficiency (MIM 300036) is caused by deficiency of the creatine transporter encoded by the SLC6A8 gene. Here we report three patients with this condition from Israel. These unrelated patients were evaluated for global developmental delays and language apraxia. Borderline microcephaly was noted in one of them. Diagnosis was prompted by brain magnetic resonance imaging and spectroscopy which revealed normal white matter distribution, but absence of the creatine peak in all three patients. Biochemical testing indicated normal plasma levels of creatine and guanidinoacetate, but an increased urine creatine/creatinine ratio. The diagnosis was confirmed by demonstrating absent [14]C-creatine transport in fibroblasts. Molecular studies indicated that the first patient is hemizygous for a single nucleotide change substituting a single amino acid (c.619 C > T, p.R207W). Expression studies in HeLa cells confirmed the causative role of the R207W substitution. The second patient had a three base pair deletion in the SLC6A8 gene (c.1222_1224delTTC, p.F408del) as well as a single base change (c.1254 + 1G > A) at a splicing site in the intron-exon junction of exon 8, the latter occurring de novo. The third patient, had a three base pair deletion (c.1006_1008delAAC, p.N336del) previously reported in other patients with creatine transporter deficiency. These three patients are the first reported cases of creatine transporter deficiency in Israel. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|