Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.

TitleSpectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
Publication TypeJournal Article
Year of Publication2011
AuthorsHannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K-ichiro, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou J-W, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ
JournalAmerican journal of medical genetics. Part A
Date Published2011 Jul
KeywordsAbnormalities, Multiple, Alleles, DNA-Binding Proteins, Face, Gene Order, Genetic Testing, Genotype, Hematologic Diseases, Humans, Mutation, Neoplasm Proteins, Phenotype, Prognosis, Vestibular Diseases

Kabuki syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki syndrome is caused by mutations in MLL2, a genei that encodes a Trithorax-group histonei methyltransferasei, a protein important in the epigenetici control of active chromatini states. Here, we report on the screening of 110 families with Kabuki syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNAi was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiencyi. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renali anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genesi for Kabuki syndrome.

Alternate JournalAm. J. Med. Genet. A
Citation Key936
PubMed ID21671394