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Novel PLS3 variants in X‐linked osteoporosis: Exploring bone material properties
Author(s) -
Balasubramanian Meena,
FratzlZelman Nadja,
O'Sullivan Rory,
Bull Mary,
FA Peel Nicola,
Pollitt Rebecca C,
Jones Rebecca,
Milne Elizabeth,
Smith Kath,
Roschger Paul,
Klaushofer Klaus,
Bishop Nicholas J
Publication year - 2018
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.38830
Subject(s) - osteoporosis , etiology , medicine , genetic testing , genetic counseling , pediatrics , pathology , genetics , biology
Background Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone‐mass. Methods Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients. Results Patient 1: 40‐year old adult male diagnosed with IJO in childhood who re‐presented with a hip fracture as an adult. Genetic analysis identified a pathogenic PLS3 hemizygous variant, c.1765del in exon 16. Patient 2: 15‐year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited PLS3 pathogenic c.1295T>A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation. Discussion We propose that genetic testing for PLS3 should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype. Conclusion This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for PLS3 . Through analysis of bone material properties in Patient 2, we can conclude that PLS3 does have a role in bone mineralisation.