The Multiple Sulfatase Deficiency Gene Encodes an Essential and Limiting Factor for the Activity of Sulfatases

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• 作者：Maria Pia Cosma ; Stefano Pepe ; Ida Annunziata ; Robert F. Newbold ; Markus Grompe ; Giancarlo Parenti and Andrea Ballabio
• 刊名：Cell
• 出版年：2003
• 出版时间：16 May 2003
• 年：2003
• 卷：113
• 期：4
• 页码：445-456
• 全文大小：598 K

文摘

In multiple sulfatase deficiency (MSD), a human inherited disorder, the activities of all sulfatases are impaired due to a defect in posttranslational modification. Here we report the identification, by functional complementation using microcell-mediated chromosome transfer, of a gene that is mutated in MSD and is able to rescue the enzymatic deficiency in patients' cell lines. Functional conservation of this gene was observed among distantly related species, suggesting a critical biological role. Coexpression of SUMF1 with sulfatases results in a strikingly synergistic increase of enzymatic activity, indicating that SUMF1 is both an essential and a limiting factor for sulfatases. These data have profound implications on the feasibility of enzyme replacement therapy for eight distinct inborn errors of metabolism.