Novel SLC5A6 mutations lead to B lymphocyte maturation defects with metabolic abnormality rescuable by biotin replenishment

• DOI: 10.1016/j.clim.2023.109855
• Publication Date: 2023-11-28T17:06:40Z
• Authors: Chu-Han Hsieh; Ju Lee; Hsiang-Hsuan Sung; Ya-Fang Huang; Yu-Sian Ding; Chia-Yi Li; Chia-Liang Yen; Chao-Kai Hsu; Chun-Keung Yu; Hsin-Ying Hsieh; Michael Warren Hu...; Peng-Chieh Chen; Chi-Chang Shieh
• Keywords: Biotin deficiency; B vitamins

We characterized a family diagnosed with immunodeficiency disease presenting low immunoglobulin levels and skin dyskeratosis. Exome sequencing revealed compound heterozygous missense variants in SLC5A6, the gene encoding cellular sodium-dependent multivitamin transporter (SMVT) responsible for transporting vitamins, including biotin (vitamin B7). showed that deficiency was caused by SLC5A6 resulting defective B cell differentiation antibody deficiency. Altered metabolic profiles, aberrant mitochondrial respiration reliance on glycolysis, may underlie failure plasma maturation. Replenishment of improved maturation recovered producing activity patient CRISPR-Cas9 gene-edited mouse model bearing patient-specific variant. Our results demonstrate critical role reprogramming cells nominate as causative be treated replenishment.