title: Isolation and characterization of a human gene containing a nuclear localization signal from the critical region for velo-cardio-facial syndrome on 22q11.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA.
authors.forename: B
authors.initials: B
authors.lastname: Funke
authors.forename: A
authors.initials: A
authors.lastname: Puech
authors.forename: B
authors.initials: B
authors.lastname: Saint-Jore
authors.forename: R
authors.initials: R
authors.lastname: Pandita
authors.forename: A
authors.initials: A
authors.lastname: Skoultchi
authors.forename: B
authors.initials: B
authors.lastname: Morrow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019465:Craniofacial Abnormalities / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins; D012269:Ribosomal Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: C115777:MRPL40 protein, human; D024101:Mitochondrial Proteins; C485463:Mrpl40 protein, mouse; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D012269:Ribosomal Proteins