Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis

Alessandra Pangrazio, Alessandro Puddu, Manuela Oppo, Maria Valentini, Luca Zammataro, Ashok Vellodi, Blanca Gener, Isabel Llano-Rivas, Jamal Raza, Irum Atta, Paolo Vezzoni, Andrea Superti-Furga, Anna Villa, Cristina Sobacchi

Research output: Contribution to journalArticlepeer-review


Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions.

Original languageEnglish
Pages (from-to)122-126
Number of pages5
Publication statusPublished - 2014


  • CTSK
  • Differential diagnosis
  • Exome sequencing
  • Sclerosing bone disorder
  • Therapy

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology


Dive into the research topics of 'Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis'. Together they form a unique fingerprint.

Cite this