MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

[kabuki syndrome]

Recently , pathogenic variants in the MLL 2 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 MLL 2 . All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL 2 -Kabuki score 0 -10 ). Sequencing of the full coding region and intron-exon boundaries of MLL 2 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-db SNP 132 variants of clinically unknown relevance , were identified . Patients with likely pathogenic nonsense or missense MLL 2 mutations were usually more severely affected (median 'MLL 2 -Kabuki score ' of 6 ) as compared to the patients without MLL 2 mutations (median 'MLL 2 -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 .

Diseases
Validation

Diseases presenting "positive patients" symptom

allergic bronchopulmonary aspergillosis

cadasil

cholangiocarcinoma

cowden syndrome

esophageal squamous cell carcinoma

heparin-induced thrombocytopenia

hodgkin lymphoma, classical

kabuki syndrome

kallmann syndrome

primary effusion lymphoma

sneddon syndrome

typhoid

waldenström macroglobulinemia

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