American Journal of Medical Genetics 57514-522 (1995) z VELO-CARDIO-FACIAL SYNDROME: FREQUENCY AND EXTENT OF zyxwv 22qll DELETIONS. Elizabeth A. Lindsay, Rosalie Goldberg, Vesna Jurecic, Bernice Morrow, Christine Carlson, Raju S. Kucherlapati, Robert J. Shprintzen and Antonio Baldini. Department of Molecular and Human Genetics and Human Genome Center, Baylor College of Medicine, Houston, zyxwvu TX I(E.A.L., V.J., A.B.). The Center for Craniofacial Disorders and the Department of Plastic Surgery and Molecular Genetics, Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY (R.G., zyxwvutsrqpo R.J. S.) zyxwvu . Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY (B.M. , C.C., R.S.K.) . Velo-cardio-facial (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phenotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH) . In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions. KEY WORDS: Velo-cardio-facial syndrome, deletions 22q11.2, haploinsufficiency syndrome. zyxwvutsrqp 0 zyxwvutsrq 1995 Wiley-Liss, Inc. INTRODUCTION Velo-cardio-facial syndrome (VCFS) , [Shprintzen et al., 1978; 1981; Goldberg et al., 1985; Goldberg et al., 19931 is characterized by cardiac anomalies, characteristic face, cleft palate, and over 30 other manifestations. The affected individuals show a wide spectrum of phenotypes. According to Shprintzen et al. [1985], VCFS is the most frequent syndrome of clefting, accounting for 8.1% of children with palatal clefts. Using a set of probes which detected deletions in DiGeorge anomaly (DGA) patients, Scambler et al. [19921 demonstrated deletions in all of 5 VCFS patients tested, Driscoll et al. [1992] demonstrated deletions in 14 out of 15 VCFS patients tested; Goldberg et al. [19931 demonstrated a deletion in all 9 VCFS patients tested; Kelly et al. [19931 reported deletions in all of 12 cases tested. Some of the patients were studied in more than one of these reports. In a Address reprint requests to: Antonio Baldini, M.D., Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA. 0 1995 Wiley-Liss, Inc.