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J Hum Genet. 2018 Aug;63(8):923-926. doi: 10.1038/s10038-018-0472-5. Epub 2018 Jun 8.

A novel frameshift deletion in PLS3 causing severe primary osteoporosis.

Author information

1
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. alice.costantini@ki.se.
2
Department of Orthopaedics, "Aghia Sophia" Children's Hospital, Athens, Greece.
3
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
4
Neonatal Special Care Unit General Hospital of Chania, Crete, Greece.
5
Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland.
6
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
7
Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
8
Department of Bone and Mineral Metabolism, Institute of Child Health, "Aghia Sophia" Children's Hospital, Athens, Greece.

Abstract

Mutations in the gene encoding plastin-3, PLS3, have recently been associated to severe primary osteoporosis. The molecular function of plastin-3 is not fully understood. Since PLS3 is located on the X chromosome, males are usually more severely affected than females. PLS3 mutations have thus far been reported in approximately 20 young patients with low bone mineral density (BMD). We describe an 8-year-old Greek boy with severe primary osteoporosis with multiple vertebral compression fractures and one low-energy long bone fracture. His clinical manifestations were consistent with osteogenesis imperfecta, including blue sclerae, joint hypermobility, low bone mineral density, kyphosis, bilateral conductive hearing loss, and mild dysmorphic features. The family history was negative for primary osteoporosis. COL1A1 and COL1A2 mutations were excluded by Sanger sequencing. However, Sanger sequencing of PLS3 led to the identification of a de novo frameshift deletion, NM_005032: c.1096_1100delAACTT, p.(Asn366Serfs*5), in exon 10 confirming the diagnosis of PLS3 osteoporosis. In conclusion, we describe a novel frameshift deletion in PLS3 causing severe primary osteoporosis in a boy. Our finding highlights the clinical overlap between type I collagen and PLS3-related skeletal fragility and underscores the importance of PLS3 screening in patients with multiple fractures to enable proper genetic counseling.

PMID:
29884797
DOI:
10.1038/s10038-018-0472-5
[Indexed for MEDLINE]

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