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.
Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers†
Article first published online: 14 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 12, pages 3042–3049, December 2011
How to Cite
Zaki, M. S., Sattar, S., Massoudi, R. A. and Gleeson, J. G. (2011), Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers. Am. J. Med. Genet., 155: 3042–3049. doi: 10.1002/ajmg.a.34173
- Issue published online: 21 NOV 2011
- Article first published online: 14 OCT 2011
- Manuscript Accepted: 29 MAY 2011
- Manuscript Received: 7 DEC 2010
- intellectual disability;
- retinal blindness;
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.