Copy number variations on chromosome 4q26-27 are associated with Cantu syndrome.
BACKGROUND
Cantu syndrome is a rare condition which is characterized clinically by hypertrichosis, cardiomegaly and bone abnormalities. Inherited hypertrichoses are very rare human disorders whose incidence has been estimated as low as 1 in 1 billion. The genetic basis of hypertrichosis is largely unknown, and currently no single gene has been directly implicated in its pathogenesis, although position effects have been reported.


METHODS
We analyzed the DNA of a patient with Cantu syndrome on the Affymetrix Cytogenetics Whole-Genome 2.7M array for copy number variations (CNVs). We then performed genomic copy number quantification using qPCR, and finally we performed gene expression analysis in the hair follicle for the genes lying within and around the region of the duplication.


RESULTS
We identified a 375 kb duplication on chromosome 4q26-27. The duplication region encompassed three genes, which included MYOZ2, USP53 and FABP2. MYOZ2 and USP53 are known to be highly expressed in the cardiac muscle, and we found that USP53 is expressed in the hair follicle.


CONCLUSIONS
We propose that CNVs involving chromosome 4q26-27 may be associated with Cantu syndrome. CNVs spanning several genes may help define the molecular basis of syndromes which have unrelated clinical features.
Department of Dermatology, Columbia University, New York, NY 10032, USA.
Mazen
M
Kurban
Chong Ae
CA
Kim
Maija
M
Kiuru
Katherine
K
Fantauzzo
Rita
R
Cabral
Ossama
O
Abbas
Brynn
B
Levy
Angela M
AM
Christiano
D000293:Adolescent; D001483:Base Sequence; D006332:Cardiomegaly / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics; D050556:Fatty Acid-Binding Proteins; D005260:Female; D020869:Gene Expression Profiling; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D018859:Hair Follicle; D006801:Humans; D006983:Hypertrichosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods; D064570:Ubiquitin-Specific Proteases
D002352:Carrier Proteins; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; C419779:MYOZ2 protein, human; D009124:Muscle Proteins; D010450:Endopeptidases; C579192:USP53 protein, human; D064570:Ubiquitin-Specific Proteases