The C20orf133 gene is disrupted in a patient with Kabuki syndrome.
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.


CONCLUSIONS
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.
Maas
Nicole M C
NM
Centre for Human Genetics, University of Leuven, Leuven, Belgium.
Van de Putte
Tom
T
Melotte
Cindy
C
Francis
Annick
A
Schrander-Stumpel
Constance T R M
CT
Sanlaville
Damien
D
Genevieve
David
D
Lyonnet
Stanislas
S
Dimitrov
Boyan
B
Devriendt
Koenraad
K
Fryns
Jean-Pierre
JP
Vermeesch
Joris R
JR
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002890:Chromosomes, Human, Pair 20 / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D045643:DNA Repair Enzymes; D005091:Exons / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006867:Hydrolases; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity; D010641:Phenotype; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
C404492:FLRT3 protein, human; C523332:MACROD2 protein, human; C523333:Macrod2 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D014157:Transcription Factors; D006867:Hydrolases; D045643:DNA Repair Enzymes