a wide spectrum of clinical and brain mri findings in patients with slc19a3 mutations广泛的临床和患者的脑部mri发现slc19a3突变.pdfVIP

Yamada et al. BMC Medical Genetics 2010, 11:171 /1471-2350/11/171 RESEARCH ARTICLE Open Access A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations 1 2 3 2 4 2 Kenichiro Yamada , Kiyokuni Miura , Kenju Hara , Motomasa Suzuki , Keiko Nakanishi , Toshiyuki Kumagai , 1 1 5 6 1* Naoko Ishihara , Yasukazu Yamada , Ryozo Kuwano , Shoji Tsuji , Nobuaki Wakamatsu Abstract Background: SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke’s-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases. Methods: We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions. Results: Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G C, [p.E320Q]) in SLC19A3 was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient. Conclusion: Our cases broaden the phenotypic spectrum of disorders associ