• Open Access

Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers

Authors

  • Maha S. Zaki,

    Corresponding author
    1. Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt
    • Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, El-Tahrir Street, Dokki, Cairo 12311, Egypt.
    Search for more papers by this author
  • Shifteh Sattar,

    1. Neurogenetics Laboratory, Department of Neurosciences and Pediatrics, Howard Hughes Medical Institute, University of California, San Diego, California
    Search for more papers by this author
  • Rustin A. Massoudi,

    1. Neurogenetics Laboratory, Department of Neurosciences and Pediatrics, Howard Hughes Medical Institute, University of California, San Diego, California
    Search for more papers by this author
  • Joseph G. Gleeson

    1. Neurogenetics Laboratory, Department of Neurosciences and Pediatrics, Howard Hughes Medical Institute, University of California, San Diego, California
    Search for more papers by this author

  • How to Cite this Article: Zaki MS, Sattar S, Massoudi RA, Gleeson JG. 2011. Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers. Am J Med Genet Part A 155: 3042–3049.

Abstract

Disorders within the “ciliopathy” spectrum include Joubert (JS), Bardet–Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum. © 2011 Wiley Periodicals, Inc.

Ancillary