Hang Lei1, Zhongying Wang2, Yuqing Wang1, Dong Xiang2, Xuefeng Wang1, Xiaohong Cai1. 1. Blood Transfusion Department, "Ruijin" Hospital, Medical School of Shanghai "Jiao Tong" University, Shanghai, China. 2. Blood Group Reference Laboratory, Shanghai Blood Center, Shanghai, China.
Abstract
BACKGROUND: Mutations of the ABO gene may cause the dysfunction of ABO glycosyltransferase (GT) that can result in weak ABO phenotypes. Here, we identified two novel weak ABO subgroup alleles and explored their mechanisms that caused Ael and Bel phenotypes. MATERIALS AND METHODS: The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of the ABO gene. The role of the novel mutations were evaluated by a three-dimensional model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. RESULTS: We identified a mutation c. 955C>G (p. L319V) of A allele in an Ael subject and a mutation c. 272T>C (p. L91P) of B allele in a Bel subject. In silico analysis showed that the mutation p. L319V of the A allele and p. L91P of the B allele may change the local conformation of GT and impair the catalysis of H to A or B antigen conversion. In vitro expression study showed that mutation p. L319V impaired H to A antigen conversion, although it did not affect the expression of glycosyltransferase A. CONCLUSIONS: Two novel "el"-type ABO subgroup alleles were identified. Both of the two novel mutations can change the local conformation of GTs and reduce protein stability. GTA mutation p. L319V can impair the conversion from H to A antigen and causes the Ael phenotype.
BACKGROUND: Mutations of the ABO gene may cause the dysfunction of ABO glycosyltransferase (GT) that can result in weak ABO phenotypes. Here, we identified two novel weak ABO subgroup alleles and explored their mechanisms that caused Ael and Bel phenotypes. MATERIALS AND METHODS: The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of the ABO gene. The role of the novel mutations were evaluated by a three-dimensional model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined. RESULTS: We identified a mutation c. 955C>G (p. L319V) of A allele in an Ael subject and a mutation c. 272T>C (p. L91P) of B allele in a Bel subject. In silico analysis showed that the mutation p. L319V of the A allele and p. L91P of the B allele may change the local conformation of GT and impair the catalysis of H to A or B antigen conversion. In vitro expression study showed that mutation p. L319V impaired H to A antigen conversion, although it did not affect the expression of glycosyltransferase A. CONCLUSIONS: Two novel "el"-type ABO subgroup alleles were identified. Both of the two novel mutations can change the local conformation of GTs and reduce protein stability. GTA mutation p. L319V can impair the conversion from H to A antigen and causes the Ael phenotype.
Authors: Annika K Hult; Mark H Yazer; René Jørgensen; Asa Hellberg; Hein Hustinx; Thierry Peyrard; Monica M Palcic; Martin L Olsson Journal: Transfusion Date: 2010-05-07 Impact factor: 3.157
Authors: Bahram Hosseini-Maaf; James A Letts; Mattias Persson; Elizabeth Smart; Pierre-Yves LePennec; Hein Hustinx; Zhihon Zhao; Monica M Palcic; Stephen V Evans; M Alan Chester; Martin L Olsson Journal: Transfusion Date: 2007-05 Impact factor: 3.157
Authors: K Ogasawara; R Yabe; M Uchikawa; N Saitou; M Bannai; K Nakata; M Takenaka; K Fujisawa; Y Ishikawa; T Juji; K Tokunaga Journal: Blood Date: 1996-10-01 Impact factor: 22.113
Authors: Sonia I Patenaude; Nina O L Seto; Svetlana N Borisova; Adam Szpacenko; Sandra L Marcus; Monica M Palcic; Stephen V Evans Journal: Nat Struct Biol Date: 2002-09