MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.
Clin Genet
; 84(6): 539-45, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-23320472
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Anomalías Múltiples
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Enfermedades Vestibulares
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Proteínas de Unión al ADN
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Cara
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Estudios de Asociación Genética
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Enfermedades Hematológicas
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Mutación
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Proteínas de Neoplasias
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Clin Genet
Año:
2013
Tipo del documento:
Article
País de afiliación:
Suiza