Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis.
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.
Scimeca
Jean-Claude
JC
Instabilité et Altérations des Génomes, UMR6549 CNRS/UNSA, Faculté de Médecine de l'Université de Nice-Sophia Antipolis, Nice, France.
Quincey
Danielle
D
Parrinello
Hugues
H
Romatet
Delphine
D
Grosgeorge
Josiane
J
Gaudray
Patrick
P
Philip
Nicole
N
Fischer
Alain
A
Carle
Georges F
GF
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*
D005819:Genetic Markers; D021122:Protein Subunits; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases