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Eosinophilic peroxidase deficiency: Identification of a point mutation (D648N) and prediction of structural changes
Author(s) -
Nakagawa Toshimasa,
Ikemoto Toshiyuki,
Takeuchi Tohru,
Tanaka Keitaro,
Tanigawa Nobuhiko,
Yamamoto Daisuke,
Shimizu Akira
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10
Subject(s) - eosinophil peroxidase , asparagine , biology , transition (genetics) , mutation , peroxidase , point mutation , amino acid , biochemistry , aspartic acid , microbiology and biotechnology , genetics , gene , enzyme
ABSTRACT Hereditary eosinophil peroxidase (EPO; EC 1.11.1.7) deficiency is a rare abnormality without clinical symptoms characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix in eosinophils. Nearly 100 cases have been reported, but a specific mutation has been reported in only one case. We report the genetic analysis of an EPO‐deficient subject and his family. The case was found by automated blood analyzer. Sequencing of the entire coding region of the EPO gene disclosed a novel mutation, a 2060 G‐A transition (g. 2060G>A) causing an amino acid change from aspartic acid to asparagine (D648N). Both the son and daughter of the propositus inherited the G‐A transition, and in vitro expression experiments suggest this transition is responsible for the deficiency. We then analyzed the location of the affected amino acid within this molecule using a structural model of EPO based on myeloperoxidase (MPO). Asn648 is on the inside of the molecule; changing D to N would cause loss of the electrostatic interaction with Arg146 which is crucial for disulfide bonds of the light chain in the N terminus. Hum Mutat 17:235–236, 2001. © 2001 Wiley‐Liss, Inc.