Related resources
Full-text held externally
- PMID: 21671394
- UKPMCID: 21671394
- DOI: 10.1002/ajmg.a.34074
Search for item elsewhere
University researcher(s)
Academic department(s)
Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
Hannibal, Mark C; Buckingham, Kati J; Ng, Sarah B; Ming, Jeffrey E; Beck, Anita E; McMillin, Margaret J; Gildersleeve, Heidi I; Bigham, Abigail W; Tabor, Holly K; Mefford, Heather C; Cook, Joseph; Yoshiura, Koh-ichiro; Matsumoto, Tadashi; Matsumoto, Naomichi; Miyake, Noriko; Tonoki, Hidefumi; Naritomi, Kenji; Kaname, Tadashi; Nagai, Toshiro; Ohashi, Hirofumi; Kurosawa, Kenji; Hou, Jia-Woei; Ohta, Tohru; Liang, Deshung; Sudo, Akira; Morris, Colleen A; Banka, Siddharth; Black, Graeme C; Clayton-Smith, Jill; Nickerson, Deborah A; Zackai, Elaine H; Shaikh, Tamim H; Donnai, Dian; Niikawa, Norio; Shendure, Jay; Bamshad, Michael J
American journal of medical genetics. Part A. 2011;155A(7):1511-6.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 21671394
- UKPMCID: 21671394
- DOI: 10.1002/ajmg.a.34074
Abstract
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 gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin 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 DNA 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 haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal 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 genes for Kabuki syndrome.
Bibliographic metadata
- Hannibal, Mark C
- Buckingham, Kati J
- Ng, Sarah B
- Ming, Jeffrey E
- Beck, Anita E
- McMillin, Margaret J
- Gildersleeve, Heidi I
- Bigham, Abigail W
- Tabor, Holly K
- Mefford, Heather C
- Cook, Joseph
- Yoshiura, Koh-ichiro
- Matsumoto, Tadashi
- Matsumoto, Naomichi
- Miyake, Noriko
- Tonoki, Hidefumi
- Naritomi, Kenji
- Kaname, Tadashi
- Nagai, Toshiro
- Ohashi, Hirofumi
- Kurosawa, Kenji
- Hou, Jia-Woei
- Ohta, Tohru
- Liang, Deshung
- Sudo, Akira
- Morris, Colleen A
- Banka, Siddharth
- Black, Graeme C
- Clayton-Smith, Jill
- Nickerson, Deborah A
- Zackai, Elaine H
- Shaikh, Tamim H
- Donnai, Dian
- Niikawa, Norio
- Shendure, Jay
- Bamshad, Michael J
- 1R01HD048895, NICHD NIH HHS, United States
- 1RC2HG005608, NHGRI NIH HHS, United States
- 5K23HD057331, NICHD NIH HHS, United States
- 5R01HG004316, NHGRI NIH HHS, United States
- 5R01HL094976, NHLBI NIH HHS, United States
- 5R21HG004749, NHGRI NIH HHS, United States
- HHSN273200800010C, PHS HHS, United States
- K99 HG004316-01, NHGRI NIH HHS, United States
- R01 HD048895-06, NICHD NIH HHS, United States
- R01 HL094976-02, NHLBI NIH HHS, United States
- R01NS35102, NINDS NIH HHS, United States
- RC2 HG005608-01, NHGRI NIH HHS, United States
- T32HG00035, NHGRI NIH HHS, United States