title: Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.
abstract: A 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.
authors.affiliation: Department of Clinical Science, Division of Internal Medicine, University of Rome La Sapienza, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Letizia
authors.forename: A
authors.initials: A
authors.lastname: Taranta
authors.forename: S
authors.initials: S
authors.lastname: Migliaccio
authors.forename: C
authors.initials: C
authors.lastname: Caliumi
authors.forename: D
authors.initials: D
authors.lastname: Diacinti
authors.forename: E
authors.initials: E
authors.lastname: Delfini
authors.forename: E
authors.initials: E
authors.lastname: D'Erasmo
authors.forename: M
authors.initials: M
authors.lastname: Iacobini
authors.forename: M
authors.initials: M
authors.lastname: Roggini
authors.forename: O M E
authors.initials: OM
authors.lastname: Albagha
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: A
authors.initials: A
authors.lastname: Teti
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001224:Aspartic Acid / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D011859:Radiography; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; D018118:Chloride Channels; D012333:RNA, Messenger; D001224:Aspartic Acid