Heterogeneity in Roberts syndrome

Abstract

Roberts syndrome (RS) is a rare, autosomal recessive condition characterized primarily by growth retardation, developmental delay, and limb anomalies. Some RS patients (RS+), but not others (RS-), have an abnormality of their constitutive heterochromatin (the "RS effect"). RS+ patients also show a cellular hypersensitivity to DNA damaging agents such as mitomycin C (MMC). Lymphoblastoid cell lines from 2 unrelated RS+ patients were fused and hybrid cells examined for correction of the RS effect and MMC hypersensitivity. Neither cellular defect was corrected in the 2 hybrid cell lines examined, suggesting that these 2 patients represent a single complementation group. Fusions were also performed between one RS+ cell line and 2 different RS- cell lines. In both fusions, the hybrids demonstrated correction of both the heterochromatin abnormality and MMC hypersensitivity. These observations suggest that RS+ and RS- patients belong to different complementation groups and do not arise from the same single gene mutation.

A Roberts Syndrome Individual With Differential Genotoxin Sensitivity and a DNA Damage Response Defect

“…The RBS-affected individual showed clear evidence of chromosomal instability and increased sensitivity to IR and mitomycin-C. This finding is consistent with a previous report of increased sensitivity to DNA damaging agents, including IR, in fibroblasts derived from RBS patients (7), but differed from another report, which demonstrated that RBS cells were sensitive to several DNA damaging agents,…”

“…It has been reported that some RBS patients' cells show hypersensitivity to DNA damaging agents causing DNA dsbs, such as ionizing radiation (IR) and mitomycin C (MMC) (7,8). Another study reported hypersensitivity of RBS fibroblasts to mitomycin C and camptothecin, but not to IR (9).…”

Thrombocytopenia-absent radius syndrome: a clinical genetic study

“…18 The majority (79%) of these children have a characteristic chromosome abnormality, that is, premature centromeric separation (PCS) or "puffing" of the chromosomes caused by repulsion of the heterochromatic regions near the centromeres of chromosomes 1, 9, and 16 with splaying of the short arms of the acrocentric chromosomes and of distal Yp. 33 There is also evidence of abnormal mitosis. 18 Roberts syndrome is thought to be inherited as an autosomal recessive trait.…”

“…18 Roberts syndrome is thought to be inherited as an autosomal recessive trait. Urban et al 33 in 1998 postulated that TAR syndrome and Roberts syndrome might be part of the same condition with TAR syndrome being the milder and Roberts the severer variants.…”

Tetraphocomelia and bilateral cleft lip in a historical case of Roberts syndrome [Virchow, 1898]

“…Recent cell hybridisation experiments suggest that cases of Roberts syndrome with cytogenetic abnormalities and those without those changes do not arise from a single gene mutation [Allingham-Hawkins and Tomkins, 1995]. So far the basic genetic defect in Roberts syndrome is unknown.…”