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Primary osteoporosis without features of OI in children and adolescents: Clinical and genetic characteristics
Author(s) -
Laine Christine M.,
Koltin Dror,
Susic Miki,
Varley Talia L.,
Daneman Alan,
Moineddin Rahim,
Cole William G.,
Mäkitie Outi,
Sochett Etienne
Publication year - 2012
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35278
Subject(s) - lrp5 , osteogenesis imperfecta , medicine , osteoporosis , cohort , allele , disease , pediatrics , wnt signaling pathway , genetics , pathology , gene , biology
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. © 2012 Wiley Periodicals, Inc.