title: Primary osteoporosis without features of OI in children and adolescents: clinical and genetic characteristics.
abstract: Our aim was to characterize clinical findings and familial associations, and to examine candidate genes for disease-causing mutations in a cohort of children suffering from primary osteoporosis without features of osteogenesis imperfecta. Patients with osteoporosis and their nuclear families were studied. Medical history was reviewed. Calcium homeostasis parameters were measured and spinal radiographs obtained. BMD was determined by DXA for patients, parents and siblings. LRP5, LRP6, and PTHLH genes were sequenced. Twenty-seven patients (14 males) from 24 families were recruited. Median age at presentation was 10.1 years (range 3.3-15.6 years). One-third of the children had at least one parent with a BMD below the expected range for age. LRP5, LRP6, and PTHLH showed no causative mutations. Four polymorphisms in LRP5 were overrepresented in patients; the minor allele frequency of Q89R, V667M, N740N, and A1330V was significantly higher than in controls. Age of onset, clinical severity, and inheritance patterns are variable in children with primary osteoporosis. Several patients had evidence suggestive of familial transmission. The underlying genetic factors remain to be elucidated.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki, Finland. christine.laine@vgregion.se
authors.forename: Christine M
authors.initials: CM
authors.lastname: Laine
authors.forename: Dror
authors.initials: D
authors.lastname: Koltin
authors.forename: Miki
authors.initials: M
authors.lastname: Susic
authors.forename: Talia L
authors.initials: TL
authors.lastname: Varley
authors.forename: Alan
authors.initials: A
authors.lastname: Daneman
authors.forename: Rahim
authors.initials: R
authors.lastname: Moineddin
authors.forename: William G
authors.initials: WG
authors.lastname: Cole
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.forename: Etienne
authors.initials: E
authors.lastname: Sochett
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000150:complications; D010024:Osteoporosis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6