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Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing

Nature Genetics volume 17, pages 9295 (1997) | Download Citation

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Abstract

Several X-linked disorders affect females disproportionately or exclusively. These including focal dermal hypoplasia1,2, oral-facial-digital syndrome type I (ref. 3) and epilepsy with bilateral periventricular heterotopias4. X-linked dominant inheritance with male lethality is probably responsible for sex-limited expression of these disorders, as affected women have frequent spontaneous abortions and the sex ratio of their live offspring is often skewed5. The same inheritance pattern has been proposed for Rett syndrome6, Aicardi syndrome7 and microphthalmia with linear skin defects8, but in these sporadic conditions, evidence of male lethality is lacking. We investigated an unusual family with epilepsy and mental retardation limited to females (EFMR, ♯121250 in ref. 9); this disorder is transmitted both by females and by completely unaffected carrier males. Assignment of the EFMR disease locus (EFMR) to the X chromosome indicates that selective involvement of females in X-linked disease may in some instances result from male sparing rather than male lethality.

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Author information

Affiliations

  1. Departments of Neurology, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, 34th Street and Civic Center Boukvard, Philadelphia, Pennsylvania 19104-4399, USA.

    • Stephen G. Ryan
    • , Phillip F. Chance
    •  & Chang-Hua Zou
  2. Departments of Pediatrics, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, 34th Street and Civic Center Boukvard, Philadelphia, Pennsylvania 19104-4399, USA.

    • Stephen G. Ryan
    • , Phillip F. Chance
    • , Chang-Hua Zou
    •  & Nancy B. Spinner
  3. Departments of Pathology, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, 34th Street and Civic Center Boukvard, Philadelphia, Pennsylvania 19104-4399, USA.

    • Jeffrey A. Golden
  4. Department of Neurology, Wayne State University School of Medicine, and The Children's Hospital of Michigan, Detroit, Michigan 48201, USA.

    • Susan Smietana

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Correspondence to Stephen G. Ryan.

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DOI

https://doi.org/10.1038/ng0997-92