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Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis
Author(s) -
Scimeca JeanClaude,
Quincey Danielle,
Parrinello Hugues,
Romatet Delphine,
Grosgeorge Josiane,
Gaudray Patrick,
Philip Nicole,
Fischer Alain,
Carle Georges F.
Publication year - 2003
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.10165
Subject(s) - osteopetrosis , biology , missense mutation , genetics , protein subunit , gene , mutation , microbiology and biotechnology , exon , frameshift mutation , cancer research , immunology
Fifty percent of the infantile malignant osteopetrosis (IMO) cases reported in the literature present mutations in the TCIRG1 gene encoding the 116‐kDa osteoclast specific subunit of the vacuolar proton ATPase (ATP6I). In this study, we identified four novel mutations in a series of six IMO patients. All of these mutations correspond to single nucleotide changes and affect splice acceptor or donor sites, resulting in aberrant transcription products. We report also a missense mutation, G405R, previously described in several Costa Rican patients. This independent finding suggests that the highly conserved residue at amino acid 405 plays a critical role in the a3 subunit function. Finally, the results of this study were used to provide a prenatal diagnosis to one of the families. Hum Mutat 21:151–157, 2003 © 2003 Wiley‐Liss, Inc.