caa a22 4500 397574487 CHVBK 20180308164851.0 cr unu---uuuuu 161202e199607 xx s 000 0 eng 10.1093/hmg/5.7.1011 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.7.1011 Clustering of Mutations in the Biotin-Binding Region of Holocarboxylase Synthetase in Biotin-Responsive Multiple Carboxylase Deficiency [Elektronische Daten] [Lucie Dupuis, Alfonso Leon-Del-Rio, Daniel Leclerc, Eric Campeau, Lawrence Sweetman, Jean-Marie Saudubray, Gail Herman, K. Michael Gibson, Roy A. Gravel] Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency (MCD). We have identified six different point mutations in the HCS gene in nine patients with MCD. Two of the mutations are frequent among the MCD patients analyzed. Four of the mutations cluster in the putative biotin-binding domain as deduced from the corresponding Escherichia coli enzyme and consistent with an explanation for biotin-responsiveness based on altered affinity for biotin. The two others may define an additional domain involved in biotin-binding or biotin-mediated stabilization of the protein. © 1996 Oxford University Press Dupuis Lucie McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut Leon-Del-Rio Alfonso McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut Leclerc Daniel McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut Campeau Eric McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut Sweetman Lawrence University of Southern California School of Medicine, Department of Pediatrics and Pathology, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA aut Saudubray Jean-Marie Groupe Hospitalier Necker-Enfants Malades, Department of Pediatrics, 142 de Sevres, Paris, 77030, France aut Herman Gail Baylor College of Medicine, Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA aut Gibson K. Michael University of Texas Southwestern Medical Center and Baylor University Medical Center, Institute of Metabolic Diseases, Department of Neurology, 3812 Elm, Dallas, TX 75226, USA aut Gravel Roy A. McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut Human Molecular Genetics Oxford University Press 5/7(1996-07), 1011-1016 0964-6906 5:7<1011 1996 5 hmg https://doi.org/10.1093/hmg/5.7.1011 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.7.1011 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dupuis Lucie McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Leon-Del-Rio Alfonso McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Leclerc Daniel McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Campeau Eric McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Sweetman Lawrence University of Southern California School of Medicine, Department of Pediatrics and Pathology, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA aut NATIONALLICENCE 700 1- Saudubray Jean-Marie Groupe Hospitalier Necker-Enfants Malades, Department of Pediatrics, 142 de Sevres, Paris, 77030, France aut NATIONALLICENCE 700 1- Herman Gail Baylor College of Medicine, Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA aut NATIONALLICENCE 700 1- Gibson K. Michael University of Texas Southwestern Medical Center and Baylor University Medical Center, Institute of Metabolic Diseases, Department of Neurology, 3812 Elm, Dallas, TX 75226, USA aut NATIONALLICENCE 700 1- Gravel Roy A. McGill University, Departments of Biology, Human Genetics and Pediatrics, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine W., Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/7(1996-07), 1011-1016 0964-6906 5:7<1011 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford