講演情報
[O24-4]A novel compound heterozygous variant of SLC5A6 associated with SMVT deficiency with brain cyst during fetal period
○宇津野 泰弘1, 濱中 耕平1, 濱田 恵輔2, 土本 啓嗣3, 砂田 哲4, 板井 俊幸1,5, 土田 奈緒美1, 内山 由理1, 藤田 京志1, 宮武 聡子1, 三澤 計治1, 水口 剛1, 緒方 一博2, 松本 直通1 (1.横浜市立大学大学院 医学研究科 遺伝学教室, 2.横浜市立大学大学院 医学研究科 生化学教室, 3.高知医療センター 小児科, 4.倉敷中央病院 小児科, 5.テキサス大学ヒューストン医療科学センター)
Sodium-dependent multivitamin transporter (SMVT) is a transmembrane protein encoded by SLC5A6. SMVT is expressed in various tissues and involved in the uptake of biotin, pantothenic acid, and lipoic acid. Biallelic pathogenic SLC5A6 variants are known to cause SMVT deficiency, which is characterized by a wide range of phenotype and well responsiveness to treatment with biotin, pantothenic acid, and alpha-lipoic acid. Phenotypes that have been reported include abnormal brain magnetic resonance imaging (MRI) findings, gastrointestinal bleeding and so forth. Only 7 variants have been reported (Human Gene Mutation Database Professional as of June 6, 2022). Here, we report novel compound heterozygous variant in SLC5A6 in a family with three affected siblings (two of three are monochorionic diamniotic twins) with abnormal fetal brain ultrasound findings like porencephaly: NM_021095.4:c.[221C＞T];[642G＞C] p.[(Ser74Phe)];[(Gln214His)] by whole-exome sequencing. Brain MRI at one month of age confirmed that three affected siblings have brain cysts and twin siblings have white matter anomalies. Analysis of protein structure predicted by AlphaFold2 suggests that both Ser74Phe and Gln214His may cause steric hindrance and lead to structural instability. Since SMVT deficiency is treatable with replacement of biotin, pantothenic acid, and alpha-lipoic acid, early diagnosis may improve outcome. This study is the first report of describing symptoms about SMVT deficiency during fetal period and indicates that some cases of SMVT deficiency can be diagnosed in the early postnatal period.