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 "common cause" symptom

achondroplasia

acute rheumatic fever

adrenomyeloneuropathy

allergic bronchopulmonary aspergillosis

alpha-thalassemia

aniridia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

child syndrome

coats disease

congenital adrenal hyperplasia

congenital toxoplasmosis

cushing syndrome

erdheim-chester disease

esophageal adenocarcinoma

esophageal squamous cell carcinoma

fabry disease

familial hypocalciuric hypercalcemia

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

lamellar ichthyosis

legionellosis

liposarcoma

locked-in syndrome

malignant atrophic papulosis

neonatal adrenoleukodystrophy

neuralgic amyotrophy

pendred syndrome

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

scrub typhus

systemic capillary leak syndrome

thoracic outlet syndrome

typhoid

von hippel-lindau disease

wiskott-aldrich syndrome

zellweger syndrome

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