Novel assay for Roberts syndrome assigns variable phenotypes to one complementation group

Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by heterogeneous clinical features, the most notable being tetraphocomelia, cleft lip, and cleft palate. Cells derived from most RS patients exhibit a bnormal cytogenetic and cellular phenotypes that include the premature sepa ration of para- and pericentromeric heterochromatin visible on C-banded met aphase chromosomes, a phenomenon referred to as heterochromatic splaying. P reviously, it was shown that these abnormal phenotypes can be complemented following somatic cell hybridization between RS cells and control cells. In the current study, a permanent cell line was established from a new RS pat ient with a more severe phenotype than represented by previously establishe d cells in culture, With a newly developed assay designed to facilitate rap id evaluation of in vitro complementation, we assigned this new patient to the same genetic complementation group defined by other, less severely affe cted patients. The results demonstrate that a single complementation group defines RS patients with heterochromatic splaying regardless of clinical se verity. Am. J, Med, Genet, 93:223-229, 2000, (C) 2000 Wiley-Liss, Inc.