title: Osteoporosis caused by mutations in PLS3: clinical and bone tissue characteristics.
abstract: Mutations in PLS3 have been identified as a cause of bone fragility in children, but the bone phenotype associated with PLS3 mutations has not been reported in detail. PLS3 is located on the X chromosome and encodes the actin-binding protein plastin 3. Here we describe skeletal findings in 4 boys from 2 families with mutations in PLS3 (c.994_995delGA; p.Asp332* in family 1; c.1433T > C; p.Leu478Pro in family 2). When first evaluated between 4 and 8 years of age, these boys had a history of one to four long-bone fractures. Mild vertebral compression fractures were identified in each boy. No obvious extraskeletal disease manifestations were present. Lumbar spine areal bone mineral density (LS-aBMD) Z-scores ranged from -1.7 to -3.5, but height was normal. Iliac bone histomorphometry in 2 patients showed low trabecular bone volume and a low osteoid maturation time but normal bone formation rate and osteoclast surface. Quantitative backscattered electron imaging (qBEI) did not reveal a major abnormality in bone mineralization density distribution. The 2 boys from family 1 received oral alendronate for 6 years, which normalized LS-aBMD. The mothers of the 4 boys did not have a history of fractures and had normal LS-aBMD. However, one of these mothers had low bone mass at the distal radius, as measured by peripheral quantitative computed tomography (pQCT). In conclusion, hemizygous mutations in PLS3 are associated with osteoporosis and bone fragility in childhood, but in contrast to bone fragility caused by mutations in collagen type I encoding genes, there is no hypermineralization of mineralized bone matrix.
authors.affiliation: Department of Human Genetics, Faculty of Medicine, McGill University and Genome Quebec Innovation Center, Montreal, Quebec, Canada.
authors.forename: Somayyeh
authors.initials: S
authors.lastname: Fahiminiya
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Hadil
authors.initials: H
authors.lastname: Al-Jallad
authors.forename: Pierre
authors.initials: P
authors.lastname: Moffatt
authors.forename: John
authors.initials: J
authors.lastname: Mort
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D000328:Adult; D015519:Bone Density; D002648:Child; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010024:Osteoporosis / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin
keywords: BONE BRITTLENESS; MINERALIZATION; OSTEOGENESIS IMPERFECTA; PLASTIN 3; QUANTITATIVE BACKSCATTERED ELECTRON IMAGING