Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis

✍ Scribed by Jean-Claude Scimeca; Danielle Quincey; Hugues Parrinello; Delphine Romatet; Josiane Grosgeorge; Patrick Gaudray; Nicole Philip; Alain Fischer; Georges F. Carle

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 208 KB
• Volume: 21
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.10165

✦ Synopsis

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.