Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears1,2,3. Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evident, intellect is usually normal in this syndrome. We report here that individuals with this disorder show marked locus heterogeneity, and we identify mutations in five separate genes: ORC1, ORC4, ORC6, CDT1 and CDC6. All of these genes encode components of the pre-replication complex, implicating defects in replication licensing as the cause of a genetic syndrome with distinct developmental abnormalities.
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We thank the subjects and their families for participation in this study and all clinicians for contributing samples not included in this manuscript. Also the late Robert J. Gorlin for contributing individual P3 to the study; E.S. Gray for pathology; M. Ansari, S. McKay, S.D. van der Velde-Visser, T.H. Merkx, S. Devroy and the MRC HGU core sequencing service for advice and technical support; E. Maher and colleagues for cytogenetic advice and assistance; and V. van Heyningen, N. Hastie, D. Fitzpatrick, I. Jackson and J. Blow for discussions and comments. This work was supported by funding from the MRC and Lister Institute of Preventative Medicine. A.P.J. is an MRC Senior Clinical Fellow and Lister Institute Prize fellow.
The authors declare no competing financial interests.
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