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Somatic mosaicism and the phenotypic expression of COL2A1 mutations

Authors

  • Sonali Nagendran,

    1. Department of Ophthalmology, Addenbrooke's Hospital, Cambridge, UK
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  • Allan J. Richards,

    1. Department of Molecular Genetics, Addenbrooke's Hospital, Cambridge, UK
    2. Department of Pathology, University of Cambridge, Cambridge, UK
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  • Annie McNinch,

    1. Department of Molecular Genetics, Addenbrooke's Hospital, Cambridge, UK
    2. Department of Pathology, University of Cambridge, Cambridge, UK
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  • Richard N. Sandford,

    Corresponding author
    1. Department of Clinical Genetics, Addenbrooke's Hospital, Cambridge, UK
    • Richard N. Sandford, Department of Clinical Genetics, Box 134, Level 6, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

      Martin P. Snead, Vitreoretinal Service, Department of Ophthalmology, BOX 41, Cambridge University NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.

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  • Martin P. Snead

    Corresponding author
    1. Department of Ophthalmology, Addenbrooke's Hospital, Cambridge, UK
    2. Department of Pathology, University of Cambridge, Cambridge, UK
    • Richard N. Sandford, Department of Clinical Genetics, Box 134, Level 6, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

      Martin P. Snead, Vitreoretinal Service, Department of Ophthalmology, BOX 41, Cambridge University NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.

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  • How to Cite this Article: Nagendran S, Richards AJ, McNinch A, Sandford RN, Snead MP. 2012. Somatic mosaicism and the phenotypic expression of COL2A1 mutations. Am J Med Genet Part A. 158A:1204–1207.

Abstract

Mutations in COL2A1, the gene for type II-collagen, can result in a wide variety of phenotypes depending upon the nature of the mutation. Dominant negative mutations tend to result in severe and often lethal skeletal dysplasias such as achondrogenesis type 2, Kniest dysplasia, and spondyloepiphyseal dysplasia congenita. Stickler syndrome, a condition characterized by ophthalmological and orofacial features, deafness and arthritis, usually, but not exclusively, results from haploinsufficiency. Overlapping features of all these disorders can also be seen in the same family. Rare reports have demonstrated that phenotypic variability can be explained in some families by somatic mosaicism. Here, we describe five further examples of somatic mosaicism of COL2A1 mutations illustrating the importance of detailed clinical evaluation and molecular testing even in clinically normal parents of affected individuals. © 2012 Wiley Periodicals, Inc.

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