Bipolar disorder in an extended pedigree with a segregation pattern compatible with X-linked transmission

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Abstract
The case for a linkage between chromosome Xq27–28 and a bipolar disorder spectrum has prevailed as the most thoroughly documented in psychiatric genetics. The only reports of molecular genetic linkage to the region are obtained with the F9 gene. It is questionable whether these findings reflect linkage to the more extensively studied color blindness-G6PD area. The impact of ethnic differences has been repeatedly suggested as an explanatory factor for divergent findings with respect to the region. The population in the present study derives from a genetically isolated area. To further reduce the risk of heterogeneity, the analysis was restricted to a single extended pedigree. Investigations based on a thorough genealogical exploration revealed no suggestion of father-to-son transmission. Operationally defined criteria were applied to exclude subjects who might introduce bilineal gene flow. Diagnoses were made using translations of appropriate parts of SADS-L and SCID with the aid of family history data and systematically collected records. Using two markers, F9 and DXS548, and with a diagnostic spectrum identical to that used in the studies reporting linkage to the F9 gene, we could exclude (lod score < −2) the chromosomal region between the two markers as well as the region extending 10 cM from F9 towards the centromere and 27 cM towards the telomere.

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