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Nishimura, G., Haga, N., Kitoh, H., Tanaka, Y., Sonoda, T., Kitamura, M., Shirahama, S., Itoh, T., Nakashima, E., Oha- shi, H. and Ikegawa, S. (2005) The Phenotypic Spectrum of COL2A1 Mutations. Human Mutation, 26, 36-43. http://dx.doi.org/10.1002/humu.20179

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• TITLE: Patella Alta and Trochlea Dysplasia Is Associated with Abnormal Type II Collagen and Matrix Accumulation in Chondrocytes

  AUTHORS: Peter Storgaard Skagen, Thomas Horn, Aubrey Milunsky, David Dejour, Bente Stærgaard, Hanne Aagaard Kruse, Tom Nicolaisen

  KEYWORDS: Patella Alta; Trochlea Dysplasia; Matrix Accumulation; Endoplasmic Reticulum Storage Disease (ERSD)

  JOURNAL NAME: Microscopy Research, Vol.2 No.2, April 28, 2014

  ABSTRACT: The purpose of this study was to perform morphological and molecular analyses of articular cartilage from a 14-year-old boy with unusual cartilage lesions, patella alta and trochlea dysplasia in both knee joints and clinically examine two family members (sister, mother), also affected in their knee joints. Biopsies from the boy’s patella were used for: histological examination, Transmission Electron Microscopy (TEM) and DNA sequencing of the COL2A1 gene including Multiplex Ligation-dependent Probe Amplification (MLPA), for detection of DNA deletions and duplications. Clinical and radiological examination showed patella alta and trochlea dysplasia for the brother (type D), sister (type A) and mother (type A) with Insall-Salvati ratios of 1.50, 1.46 and 1.3. Light Microscopy (LM) of biopsies from the patient showed rhomboid chondrocytes in lacuna with deposition of protein aggregates in the ECM. TEM revealed abnormal type II collagen fibrils in aggregates and chondrocytes with abnormal matrix accumulation in rough Endoplasmic Reticulum (rER). Immunostaining showed that type II collagen was deposited intracellularly and in protein aggregates, together with type I collagen, indicating alterations in chondrocyte function and turnover of these molecules. DNA sequencing of 54 exons including extended DNA analysis with MLPA was non-conclusive. Conclusions: We suggest that patella alta and trochlea dysplasia for this patient is associated with collagen accumulation in chondrocytes, abnormal type II collagen heterofibrils in the ECM, cell death and cartilage with subnormal strength and increased risk of premature patellofemoral arthritis. A family with these disorders suggests that phenotype might be transmitted as an autosomal dominant trait.