J Pediatr Genet 2018; 07(01): 009-013
DOI: 10.1055/s-0037-1604100
Original Article
Georg Thieme Verlag KG Stuttgart · New York

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

Arya Shambhavi*
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Smrithi Salian*
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Hitesh Shah
Department of Orthopaedics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Mohandas Nair
Department of Pediatrics, Government Medical College, Kozhikode, India
,
Krishna Sharan
Department of Radiotherapy, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Dong-Kyu Jin
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Sung Yoon Cho
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
,
Mary Mathew
Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Anju Shukla
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
,
Katta M. Girisha
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
› Author Affiliations
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).
Further Information

Publication History

24 February 2017

01 June 2017

Publication Date:
13 July 2017 (eFirst)

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.

* Both the authors contributed equally to the article.


Supplementary Material