title: A co-occurrence of osteogenesis imperfecta type VI and cystinosis.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tracy
authors.initials: T
authors.lastname: Tucker
authors.forename: Tanya
authors.initials: T
authors.lastname: Nelson
authors.forename: Sandra
authors.initials: S
authors.lastname: Sirrs
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
authors.forename: Pierre
authors.initials: P
authors.lastname: Moffatt
authors.forename: Kamilla
authors.initials: K
authors.lastname: Schlade-Bartusiak
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D000293:Adolescent; D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D001483:Base Sequence; D002648:Child; D003554:Cystinosis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D020440:Gene Duplication; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D015843:Serpins / Q000235:genetics; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C111445:CTNS protein, human