Abstract
The Kabuki syndrome (KS, OMIM 147920), also known as the Niikawa–Kuroki syndrome, is a multiple congenital anomaly/mental retardation syndrome characterized by a distinct facial appearance. The cause of KS has been unidentified, even by whole-genome scan with array comparative genomic hybridization (CGH). In recent years, high-resolution oligonucleotide array technologies have enabled us to detect fine copy number alterations. In 17 patients with KS, molecular karyotyping was carried out with GeneChip 250K NspI array (Affymetrix) and Copy Number Analyser for GeneChip (CNAG). It showed seven copy number alterations, three deleted regions and four duplicated regions among the patients, with the exception of registered copy number variants (CNVs). Among the seven loci, only the region of 9q21.11-q21.12 (∼1.27 Mb) involved coding genes, namely, transient receptor potential cation channel, subfamily M, member 3 (TRPM3), Kruppel-like factor 9 (KLF9), structural maintenance of chromosomes protein 5 (SMC5) and MAM domain containing 2 (MAMDC2). Mutation screening for the genes detected 10 base substitutions consisting of seven single-nucleotide polymorphisms (SNPs) and three silent mutations in 41 patients with KS. Our study could not show the causative genes for KS, but the locus of 9q21.11-q21.12, in association with a cleft palate, may contribute to the manifestation of KS in the patient. As various platforms on oligonucleotide arrays have been developed, higher resolution platforms will need to be applied to search tiny genomic rearrangements in patients with KS.
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Acknowledgements
We are grateful to the patients and their parents for their participation in this research. We also thank Ms Yasuko Noguchi, Ms Miho Ooga and Ms Chisa Hayashida for their technical assistance. NN was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan, and was supported by SORST from Japan Science and Technology Agency (JST) (Nos. 17019055 and 19390095, respectively). KY was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Health, Labor and Welfare.
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Kuniba, H., Yoshiura, Ki., Kondoh, T. et al. Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome. J Hum Genet 54, 304–309 (2009). https://doi.org/10.1038/jhg.2009.30
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DOI: https://doi.org/10.1038/jhg.2009.30
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