TY - JOUR
T1 - A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations
AU - Yamada, Kenichiro
AU - Miura, Kiyokuni
AU - Hara, Kenju
AU - Suzuki, Motomasa
AU - Nakanishi, Keiko
AU - Kumagai, Toshiyuki
AU - Ishihara, Naoko
AU - Yamada, Yasukazu
AU - Kuwano, Ryozo
AU - Tsuji, Shoji
AU - Wakamatsu, Nobuaki
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/12/22
Y1 - 2010/12/22
N2 - 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 associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.
AB - 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 associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.
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U2 - 10.1186/1471-2350-11-171
DO - 10.1186/1471-2350-11-171
M3 - Article
C2 - 21176162
AN - SCOPUS:78650295909
VL - 11
JO - BMC Medical Genetics
JF - BMC Medical Genetics
SN - 1471-2350
IS - 1
M1 - 171
ER -