Journal Article

The Oral-Facial-Digital Syndrome Type 1 (OFD1), a Cause of Polycystic Kidney Disease and Associated Malformations, Maps to Xp22.2-Xp22.3

Sally A. Feather, Adrian S. Woolf, Dian Donnai, Sue Malcolm and Robin M. Winter

in Human Molecular Genetics

Volume 6, issue 7, pages 1163-1167
Published in print July 1997 | ISSN: 0964-6906
Published online July 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.7.1163
The Oral-Facial-Digital Syndrome Type 1 (OFD1), a Cause of Polycystic Kidney Disease and Associated Malformations, Maps to Xp22.2-Xp22.3

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Key features of the oral-facial-digital syndrome type 1 (OFD1) include malformations of the face, oral cavity and digits. In addition, the clinical phenotype often includes mental retardation and renal functional impairment. Approximately 75% of cases of OFD1 are sporadic, and the condition occurs almost exclusively in females. In familial cases, the most likely mode of inheritance is considered to be X-linked dominant with prenatal lethality in affected males. Therefore, theOFD1 gene product appears to have widespread importance in organogenesis and is essential for fetal survival. We have studied two kindreds in which the clinical course was dominated by polycystic kidney disease requiring dialysis and transplantation. Using polymorphic chromosome markers spaced at ∼10 cM intervals along the X chromosome, we mapped the disease to a region on the short arm of the X chromosome (Xp22.2-Xp22.3) spanning 19.8 cM and flanked by crossovers with the markers DXS996 and DX7S105. There was a maximum lod score of 3.32 in an ‘affecteds only’ analysis using a marker within the KAL gene (θ = 0.0), thereby confirming the location of the gene for OFD1 on the X chromosome. The remainder of the X chromosome was excluded by recombinants in affected individuals. The importance of our findings includes the definitive assignment of this male-lethal disease to the X chromosome and the mapping of a further locus for a human polycystic kidney disease. Furthermore, this mapping study suggests a possible mouse model for OFD1 as the X-linked dominant Xpl mutant, in which polydactyly and renal cystic disease occurs, maps to the homologous region of the mouse X chromosome.

Journal Article.  3060 words.  Illustrated.

Subjects: Genetics and Genomics

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