Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor

Arya Shambhavi; Smrithi Salian; Hitesh Shah; Mohandas Nair; Krishna Sharan; Dong-Kyu Jin; Sung Yoon Cho; Mary Mathew; Anju Shukla; Katta M Girisha

doi:10.1055/s-0037-1604100

Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor

J Pediatr Genet. 2018 Mar;7(1):9-13. doi: 10.1055/s-0037-1604100. Epub 2017 Jul 13.

Authors

Affiliations

¹ Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
² Department of Orthopaedics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
³ Department of Pediatrics, Government Medical College, Kozhikode, India.
⁴ Department of Radiotherapy, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
⁵ Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁶ Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

Abstract

Pycnodysostosis is an autosomal recessive skeletal dysplasia caused by pathogenic variants in the cathepsin K ( CTSK ) gene. We report seven patients from four unrelated families with this condition in whom we have identified three novel pathogenic variants, c.120 + 1G > T in intron 2, c.399 + 1G > A in intron 4, and c.148T > G (p.W50G) in exon 2, and a known variant, c.568C > T (p.Q190*) in exon 5 of CTSK . We present the clinical, radiographic, and molecular findings of all individuals with molecularly proven pycnodysostosis from the present cohort. We also report the occurrence of giant cell tumor in the skull of a patient with this condition.

Keywords: cathepsin K; giant cell tumor; pycnodysostosis.

Grants and funding

Funding This work is funded by the Department of Science and Technology through the project titled “Application of autozygosity mapping and exome sequencing to identify genetic basis of disorders of skeletal development” (SB/SO/HS/005/2014).