title: Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis.
abstract: Osteopetrosis is a heterogeneous group of inherited disorders that includes a malignant autosomal recessive form, an intermediate autosomal recessive form and autosomal dominant forms of the disease. Most malignant osteopetroses have been ascribed to mutations in the OC116 gene encoding the human a3 subunit of vacuolar H(+)-ATPase. Few cases of autosomal recessive malignant osteopetrosis have been ascribed to mutations in the chloride channel 7 gene (CLCN7), which accounts for all autosomal dominant type II cases reported to date. Up until now, however, nothing has been known regarding the molecular basis of the intermediate form of osteopetrosis (IARO). Our study of two Portuguese IARO families shows that homozygosity for ClCN7 mutations also accounts for this form of osteopetrosis. The two patients presented with spontaneous fractures in the first years of life and generalised increase of bone density. Direct sequencing of the ClCN7 gene in both patients revealed homozygosity for two mutations (G203D and P470Q). We conclude therefore that ClCN7 mutations not only account for some dominant and malignant forms but also for intermediate forms of osteopetrosis.
authors.affiliation: Department of Medical Genetics and INSERM U393, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015 Paris, France.
authors.forename: Ana Belinda
authors.initials: AB
authors.lastname: Campos-Xavier
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Saraiva
authors.forename: Letícia M
authors.initials: LM
authors.lastname: Ribeiro
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011859:Radiography
chemical_list: C097540:CLCN7 protein, human; D018118:Chloride Channels; D017931:DNA Primers