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 congenital disorders characterized by craniofacial anomalies, conotruncal heart defects, immune deficiencies, and learning disabilities. Both diseases 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. NLVCF 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 two consensus sequences for nuclear localization signals. The Nlvcf mouse homolog is 75% identical in amino acid sequence and maps to the orthologous region on mouse chromosome 16. The human NLVCF transcript is 1.3 kb in size and is expressed at varying levels in many fetal and adult tissues. Whole-mount in situ hybridization showed that Nlvcf is expressed in most structures of 9.5-dpc mouse embryos, with especially high expression in the head as well as in the first and second pharyngeal arches. NLVCF and HIRA are divergently transcribed, and their start codons lie approximately 1 kb apart in both humans and mice. Interestingly, the two genes exhibit a similar expression pattern in mouse embryos, suggesting that they may share common regulatory elements. The pattern of expression of NLVCF and its localization in the critical region suggest that NLVCF may contribute to the etiology of VCFS.