The C20orf133 gene is disrupted in a patient with Kabuki syndrome

• Published in: Journal of medical genetics Vol. 44; no. 9; pp. 562 - jmg
• Main Authors: Maas, Nicole, Van de Putte, Tom, Melotte, Cindy, Francis, Annick, Schrander-Stumpel, Constance TRM, Sanlaville, Damien, Genevieve, David, Lyonnet, Stanislas, Dimitrov, Boyan, Devriendt, Koenraad, Fryns, Jean-Pierre, Vermeesch, Joris
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-09-2007; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Abnormalities, Multiple - genetics; ADP-ribose-1′-monophosphatase; ADP-ribose-1′-monophosphate; Amino Acid Sequence; Animals; Appr-1”-P; Appr-1”-Pase; array CGH; Artificial chromosomes; BAC; bacterial artificial chromosome; Biological and medical sciences; C20orf133; CGH; CHARGE; choanal atresia; Chromatin; Chromosome rearrangements; Chromosomes, Human, Pair 20 - chemistry; Chromosomes, Human, Pair 20 - genetics; Chromosomes, Human, Pair 20 - ultrastructure; Cloning; CNV; coloboma; comparative genomic hybridisation; Congenital defects; copy-number variation; denaturating high-performance liquid chromatography; DHPLC; DNA Repair Enzymes; embryonic day; Exons - genetics; Face - abnormalities; Female; fibronectin-like domain-containing leucine-rich transmembrane protein 3; FISH; FLRT3; fluorescence in situ hybridisation; Fundamental and applied biological sciences. Psychology; Ganglia; Gene Expression Regulation, Developmental; Genes; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; heart anomalies; Humans; Hybridization; Hydrolases; Infant, Newborn; Inner ear; Intellectual disabilities; Intellectual Disability - genetics; Kabuki syndrome; Medical genetics; Medical sciences; Membrane Glycoproteins; Membrane Proteins - genetics; Mice; microdeletion; Molecular and cellular biology; Molecular Sequence Data; Mutation; National Center for Biotechnology Information; NCBI; Nervous system; Nucleic Acid Hybridization; Organ Specificity; Original; Patients; Phenotype; Phenotypes; Proteins; qPCR; quantitative PCR; retardation of growth and development and genital and ear abnormalities; reverse transcriptase; Sequence Alignment; Sequence Deletion; Sequence Homology, Amino Acid; Simple Modular Architecture Research Tool; single nucleotide polymorphism; SMART; SNP; Syndrome; TEAA; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; triethylamine acetate; UCSC; University of California Santa Cruz; Zebrafish; Human; Gene; Malformation; Kabuki make-up syndrome; Genetics; Patient; Complex syndrome
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2007.049510

Background: Kabuki syndrome (KS) is a rare, clinically recognisable, congenital mental retardation syndrome. The aetiology of KS remains unknown. Methods: Four carefully selected patients with KS were screened for chromosomal imbalances using array comparative genomic hybridisation at 1 Mb resolution. Results: In one patient, a 250 kb de novo microdeletion at 20p12.1 was detected, deleting exon 5 of C20orf133. The function of this gene is unknown. In situ hybridisation with the mouse orthologue of C20orf133 showed expression mainly in brain, but also in kidney, eye, inner ear, ganglia of the peripheral nervous system and lung. Conclusion: The de novo nature of the deletion, the expression data and the fact that C20orf133 carries a macro domain, suggesting a role for the gene in chromatin biology, make the gene a likely candidate to cause the phenotype in this patient with KS. Both the finding of different of chromosomal rearrangements in patients with KS features and the absence of C20orf133 mutations in 19 additional patients with KS suggest that KS is genetically heterogeneous.