IBMS BoneKEy | Clinical Cases
Duplication of 17p13.3 associated with an unclassified type of metaphyseal dysplasia
Erin M Shih
John M Graham
Thitiwat Chaikul
Pisit Pitukcheewanont
DOI:10.1038/bonekey.2015.137
Abstract
We report a 17p13.3 duplication detected on whole-exome sequencing (WES) analysis in a patient with an unclassified type of metaphyseal dysplasia. A 12-year-old male presented with short stature and associated genu valgum and coxa valga. Radiographic findings showed multiple lytic and sclerotic metaphyses. He had bilateral distal femoral and proximal tibial medial hemiepiphysiodesis and two bilateral triple pelvic osteotomies, after which the orthopedic surgeon noted ‘somewhat soft bones’. He also had progressive linear growth deceleration (height −2.3 s.d., weight +0.8 s.d.), upper-to-lower segment ratio of +3.5 s.d., no blue sclerae, normal cognitive function and no history of fractures. His endocrine evaluation and RMRP and COL10A1 gene sequencing were normal, but WES analysis and oligonucleotide-single-nucleotide polymorphism chromosomal microarray revealed a de novo 608-kb duplication of 17p13.3. This duplication included multiple genes including SERPINF1. SERPINF1 encodes pigment epithelium-derived factor, which has a critical role in collagen type-I binding, with haploinsufficiency resulting in severe autosomal recessive osteogenesis imperfecta. There are no reports of this gene duplication resulting in an unclassified type of metaphyseal dysplasia. However, this finding could suggest the possibility that this gene might be dosage sensitive.
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