ISOLATION AND CHARACTERIZATION OF A HUMAN GENE CONTAINING A NUCLEAR-LOCALIZATION SIGNAL FROM THE CRITICAL REGION FOR VELO-CARDIO-FACIAL SYNDROME ON 22Q11

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome are congenita l disorders characterized by craniofacial anomalies, conotruncal heart defects, immune deficiencies, and learning disabilities. Both disease s are associated with similar hemizygous 22q11. deletions, indicating that haploinsufficiency of a gene(s) in 22q11 is responsible for their etiology. We describe here a new gene called NLVCF, which maps to the critical region for VCFS on 22q11 between the genes HIRA and UFD1L. N LVCF encodes a putative protein of 206 amino acids. The coding region encompasses four exons that span a genomic interval of 3.4 kb. Coding sequence analysis revealed that NLVCF is a novel gene that contains tw o consensus sequences for nuclear localization signals. The Nlvcf mous e homolog is 75% identical in amino acid sequence and maps to the orth ologous region on mouse chromosome 1.6. The human NLVCF transcript is 1.3 kb in size and is expressed at varying levels in many fetal and ad ult tissues. Whole-mount in situ hybridization showed that Nlvcf is ex pressed in most structures of 9.5-dpc mouse embryos, with especially h igh expression in the head as well as in the first and second pharynge al arches. NLVCF and HIRA are divergently transcribed, and their start codons lie approximately 1 kb apart in both humans and mice. Interest ingly, the two genes exhibit a similar expression pattern in mouse emb ryos, suggesting that they may share common regulatory elements. The p attern of expression of NLVCF and its localization in the critical reg ion suggest that NLVCF may contribute to the etiology of VCFS. (C) 199 8 Academic Press.