MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study
(2013) Clinical Genetics : an international journal of genetics and molecular medicine — Vol. 84, n° 6, p. 539-545 (2013)
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- Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.
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Makrythanasis, P., van Bon, B., Steehouwer, M., Rodríguez-Santiago, B., Simpson, M., Dias, P., Anderlid, B., Arts, P., Bhat, M., Augello, B., Biamino, E., Bongers, E., Del Campo, M., Cordeiro, I., Cueto-González, A., Cuscó, I., Deshpande, C., Frysira, E., Izatt, L., et al. (2013). MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study. Clinical Genetics : an international journal of genetics and molecular medicine, 84(6), 539-545. https://doi.org/10.1111/cge.12081 (Original work published 2013)