title: Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis.
abstract: 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.
authors.affiliation: Instabilité et Altérations des Génomes, UMR6549 CNRS/UNSA, Faculté de Médecine de l'Université de Nice-Sophia Antipolis, Nice, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Scimeca
authors.forename: Danielle
authors.initials: D
authors.lastname: Quincey
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.forename: Delphine
authors.initials: D
authors.lastname: Romatet
authors.forename: Josiane
authors.initials: J
authors.lastname: Grosgeorge
authors.forename: Patrick
authors.initials: P
authors.lastname: Gaudray
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Georges F
authors.initials: GF
authors.lastname: Carle
mesh_terms: D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D010010:Osteoclasts / Q000145:classification / Q000378:metabolism; D010022:Osteopetrosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D010375:Pedigree; D011296:Prenatal Diagnosis; D021122:Protein Subunits / Q000235:genetics*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D021122:Protein Subunits; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases