ctip mutations cause seckel and jawad syndromesctip突变导致塞克尔梨和jawad综合症.pdfVIP

CtIP Mutations Cause Seckel and Jawad Syndromes 1. 2,3. 3 1 4¤ Per Qvist , Pablo Huertas *, Sonia Jimeno , Mette Nyegaard , Muhammad J. Hassan , Stephen P. 2 1 Jackson *, Anders D. Børglum * 1 Department of Human Genetics and Department of Biomedicine, Aarhus University, Aarhus, Denmark, 2 The Gurdon Institute and Department of Biochemistry, ´ ´ University of Cambridge, Cambridge, United Kingdom, 3 Centro Andaluz de Biologıa Molecular y Medicina Regenerativa (CABIMER) and Departamento de Genetica, Universidad de Sevilla, Sevilla, Spain, 4 Department of Biochemistry, Faculty of Biological Sciences, Quaid i Azam University, Islamabad, Pakistan Abstract Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and a unique head profile. Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5) but only three disease genes identified: the ATR, CENPJ, and CEP152 genes that control cellular responses to DNA damage. We previously mapped a Seckel syndrome locus to chromosome 18p11.31-q11.2 (SCKL2). Here, we report two mutations in the CtIP (RBBP8) gene within this locus that result in expression of C-terminally truncated forms of CtIP. We propose that these mutations are the molecular cause of the disease observed in the previously described SCKL2 family and in an additional unrelated family diagnosed with a similar form of congenital microcephaly termed Jawad syndrome. W