De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing
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- 作者：Samuel P Strom ; Reymundo Lozano ; Hane Lee ; Naghmeh Dorrani…
- 关键词：Wiedemann ; Steiner syndrome ; Clinical exome sequencing ; KMT2A ; Intellectual disability ; Developmental delay
- 刊名：BMC Medical Genetics
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：15
- 期：1
- 全文大小：654 KB
- 参考文献：1. Ng, SB, Bigham, AW, Buckingham, KJ, Hannibal, MC, McMillin, MJ, Gildersleeve, HI, Beck, AE, Tabor, HK, Cooper, GM, Mefford, HC, Lee, C, Turner, EH, Smith, JD, Rieder, MJ, Yoshiura, K, Matsumoto, N, Ohta, T, Niikawa, N, Nickerson, DA, Bamshad, MJ, Shendure, J (2010) Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 42: pp. 790-793 CrossRef
2. Miyake, N, Mizuno, S, Okamoto, N, Ohashi, H, Shiina, M, Ogata, K, Tsurusaki, Y, Nakashima, M, Saitsu, H, Niikawa, N, Matsumoto, N (2013) KDM6A point mutations cause Kabuki syndrome. Hum Mutat 34: pp. 108-110 CrossRef
3. Kleefstra, T, van Zelst-Stams, WA, Nillesen, WM, Cormier-Daire, V, Houge, G, Foulds, N, van Dooren, M, Willemsen, MH, Pfundt, R, Turner, A, Wilson, M, McGaughran, J, Rauch, A, Zenker, M, Adam, MP, Innes, M, Davies, C, López, AG, Casalone, R, Weber, A, Brueton, LA, Navarro, AD, Bralo, MP, Venselaar, H, Stegmann, SP, Yntema, HG, van Bokhoven, H, Brunner, HG (2009) Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype. J Med Genet 46: pp. 598-606 CrossRef
4. Campeau, PM, Lu, JT, Dawson, BC, Fokkema, IF, Robertson, SP, Gibbs, RA, Lee, BH (2012) The KAT6B-related disorders genitopatellar syndrome and Ohdo/SBBYS syndrome have distinct clinical features reflecting distinct molecular mechanisms. Hum Mutat 33: pp. 1520-1525 CrossRef
5. Gibson, WT, Hood, RL, Zhan, SH, Bulman, DE, Fejes, AP, Moore, R, Mungall, AJ, Eydoux, P, Babul-Hirji, R, An, J, Marra, MA, Chitayat, D, Boycott, KM, Weaver, DD, Jones, SJ (2012) Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet 90: pp. 110-118 CrossRef
6. Deardorff, MA, Bando, M, Nakato, R, Watrin, E, Itoh, T, Minamino, M, Saitoh, K, Komata, M, Katou, Y, Clark, D, Cole, KE, De Baere, E, Decroos, C, Di Donato, N, Ernst, S, Francey, LJ, Gyftodimou, Y, Hirashima, K, Hullings, M, Ishikawa, Y, Jaulin, C, Kaur, M, Kiyono, T, Lombardi, PM, Magnaghi-Jaulin, L, Mortier, GR, Nozaki, N, Petersen, MB, Seimiya, H, Siu, VM (2012) HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 489: pp. 313-317 CrossRef
7. Harakalova, M, van den Boogaard, MJ, Sinke, R, van Lieshout, S, van Tuil, MC, Duran, K, Renkens, I, Terhal, PA, de Kovel, C, Nijman, IJ, van Haelst, M, Knoers, NV, van Haaften, G, Kloosterman, W, Hennekam, RC, Cuppen, E, van Amstel HK, P (2012) X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face. J Med Genet 49: pp. 539-543 CrossRef
8. Kaiser, FJ, Ansari, M, Braunholz, D, Concepcion Gil-Rodriguez, M, Decroos, C, Wilde, JJ, Fincher, CT, Kaur, M, Bando, M, Amor, DJ, Atwal, PS, Bahlo, M, Bowman, CM, Bradley, JJ, Brunner, HG, Clark, D, Del Campo, M, Di Donato, N, Diakumis, P, Dubbs, H, Dyment, DA, Eckhold, J, Ernst, S, Ferreira, JC, Francey, LJ, Gehlken, U, Guillén-Navarro, E, Gyftodimou, Y, Hall, BD, Hennekam, R (2014) Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance. Hum Mol Genet.
9. Jones, WD, Dafou, D, McEntagart, M, Woollard, WJ, Elmslie, FV, Holder-Espinasse, M, Irving, M, Saggar, AK, Smithson, S, Trembath, RC, Deshpande, C, Simpson, MA (2012) De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet 91: pp. 358-364 CrossRef
10. Petrij, F, Giles, RH, Dauwerse, HG, Saris, JJ, Hennekam, RC, Masuno, M, Tommerup, N, van Ommen, GJ, Goodman, RH, Peters, DJ (1995) Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376: pp. 348-351 CrossRef
11. Kurotaki, N, Imaizumi, K, Harada, N, Masuno, M, Kondoh, T, Nagai, T, Ohashi, H, Naritomi, K, Tsukahara, M, Makita, Y, Sugimoto, T, Sono - 刊物主题：Human Genetics; Genetics and Population Dynamics;
- 出版者：BioMed Central
- ISSN：1471-2350
文摘
Background Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. Case presentation For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3- left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. Conclusions Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS.