Manitoba Aboriginal Kindred with Original Cerebro-Oculo-Facio-Skeletal Syndrome Has a Mutation in the Cockayne Syndrome Group B (CSB) Gene Lisiane B.

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Manitoba Aboriginal Kindred with Original Cerebro-Oculo-Facio-Skeletal Syndrome Has a Mutation in the Cockayne Syndrome Group B (CSB) Gene Lisiane B. Meira, John M. Graham, Cheryl R. Greenberg, David B. Busch, Ana T.B. Doughty, Deborah W. Ziffer, Donna M. Coleman, Isabelle Savre-Train, Errol C. Friedberg The American Journal of Human Genetics Volume 66, Issue 4, Pages 1221-1228 (April 2000) DOI: 10.1086/302867 Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 1 Patients 1 and 2 at age 5 years. They demonstrate classic COFS syndrome facial features, including microcephaly, microphthalmia with deep-set eyes, prominent nasal root, and large ear pinnae. The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 2 Survival of COFS cell lines after exposure to UV radiation. Wild-type fibroblast cell line GM1604 (unblackened squares), COFS syndrome patient 1 (blackened circles), COFS syndrome patient 3 (unblackened circles), and cells from a CS group B patient (blackened squares). Survival values are the mean of triplicate experiments. The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 3 COFS cell lines are proficient in unscheduled DNA synthesis. Quantitation of grains/nucleus in 100 non-S phase cells of a wild-type (Tel1604) cell line (blackened bars), COFS cell line TelCOFS03MA (unblackened bars), and COFS cell line TelCOFS02MA (gray bars). Grain counts are expressed as histograms and show that the COFS cell lines are proficient in unscheduled DNA synthesis. The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 4 Recovery of RNA synthesis in a wild-type cell line (Tel1604;blackened squares) and COFS cell lines TelCOFS02MA (green squares) and TelCOFS03MA (red squares). Data for a CSB mutant cell line (CS2PB; blue squares) are shown for comparison. Unirradiated or UV-irradiated (with 4 J/m2) cells were pulse-labeled with [3H] at different times after irradiation (see Material and Methods section for details). Data points represent the mean of triplicate plates. The SEM falls within the size of the symbols. The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 5 Sequence chromatograms showing the mutation found in patients with COFS syndrome. Arrows mark the position where the mutation is localized.A, Wild-type nucleotide and predicted amino acid sequence. B, Sequence of one patient with COFS syndrome; the anticipated stop codon is underlined. C, Sequence of the father of the patient depicted in B. Note the frameshift shown by the overlap of both wild-type and mutant alleles in the carrier (arrow). The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions

Figure 6 Complementation of UV radiation sensitivity in immortalized COFS cells (TelCOFS03MA). COFS and wild-type cell lines were transfected with either pSV2neo alone or cotransfected with pSV2neo and the expression vector pSLME6 carrying the CSB gene. G418-resistant clones were pooled and examined for UV radiation sensitivity. Repair-proficient line Tel1604 transfected with pSV2neo (unblackened circles) or with pSV2neo plus pSLME6 (blackened circles). COFS cells (TelCOFS03MA) transfected with pSV2neo (unblackened squares) or with pSV2neo plus pSLME6 (blackened squares). Vertical bars represent the SEM of three experiments. The American Journal of Human Genetics 2000 66, 1221-1228DOI: (10.1086/302867) Copyright © 2000 The American Society of Human Genetics Terms and Conditions