How to Cite this Article: Tucker T, Nelson T, Sirrs S, Roughley P, Glorieux FH, Moffatt P, Schlade-Bartusiak K, Brown L, Rauch F. 2012. A co-occurrence of osteogenesis imperfecta type VI and cystinosis. Am J Med Genet Part A. 158A:1422–1426.
A co-occurrence of osteogenesis imperfecta type VI and cystinosis†
Article first published online: 23 APR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 6, pages 1422–1426, June 2012
How to Cite
Tucker, T., Nelson, T., Sirrs, S., Roughley, P., Glorieux, F. H., Moffatt, P., Schlade-Bartusiak, K., Brown, L. and Rauch, F. (2012), A co-occurrence of osteogenesis imperfecta type VI and cystinosis. Am. J. Med. Genet., 158A: 1422–1426. doi: 10.1002/ajmg.a.35319
- Issue published online: 17 MAY 2012
- Article first published online: 23 APR 2012
- Manuscript Accepted: 7 JAN 2012
- Manuscript Received: 31 AUG 2011
- Shriners of North America
- recessive osteogenesis imperfecta;
- pigment epithelium-derived factor;
Osteogenesis imperfecta type VI (OI type VI) is a rare autosomal recessive disorder caused by mutations in the SERPINF1 gene that encodes pigment epithelium-derived factor (PEDF). Cystinosis is an autosomal recessive lysosomal transport disorder caused by mutations in the CTNS gene. Both SERPINF1 and CTNS are located on chromosome 17p13.3. We describe an individual presenting with both OI type VI and cystinosis. The patient was diagnosed with cystinosis at the age of 11 months and OI type VI on bone biopsy at the age of 8 years. He has sustained over 30 fractures during his lifetime, and at the age of 19 years entered end-stage renal disease and subsequent renal transplant. An Affymetrix 6.0 array was used to look for areas of loss of heterozygosity on chromosome 17. Sequencing of the SERPINF1 and CTNS genes was performed, followed by quantitative PCR and Western blot of PEDF to characterize the identified mutation. A 6.58 Mb region of homozygosity was identified on the Affymetrix 6.0 array, encompassing both the SERPINF1 and CTNS genes. Sequencing of the genes identified homozygosity for a known pathogenic CTNS mutation and for a novel in-frame duplication in SERPINF1. Skin fibroblasts produced a markedly reduced amount of SERPINF1 transcript and PEDF protein. This patient has the concurrent phenotype of two rare recessive diseases, cystinosis and OI type VI. We identified for the first time an in-frame duplication in SERPINF1 that is responsible for the OI type VI phenotype in this patient. © 2012 Wiley Periodicals, Inc.