Abstract
We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral–facial–digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.
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Acknowledgments
We would like to thank the patients and their families for their participation in the studies. This work was supported by the EU (grant no. QLRT-2001-01810) and by a ‘Partner Group’ grant from the Max Planck Society (to H.H.R and A.L.-B.). H.O. and M.F. were supported by grants from the Deutsche Forschungsgemeinschaft (DFG Om 6/2; SFB592).
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Budny, B., Chen, W., Omran, H. et al. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral–facial–digital type I syndrome . Hum Genet 120, 171–178 (2006). https://doi.org/10.1007/s00439-006-0210-5
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DOI: https://doi.org/10.1007/s00439-006-0210-5