De novo ANKRD11 and KDM1A gene mutations in a male with features of KBG syndrome and Kabuki syndrome.
KBG syndrome is a rare, autosomal dominant disorder caused by mutations or deletions leading to haploinsufficiency for the Ankrin Repeating Domain-Containing protein 11 (ANKRD11) at chromosome 16q24.3. Kabuki syndrome is caused by mutations or deletions of lysine (K)-specific methyltransferase 2D (KMT2D) and lysine-specific methylase 6A (KDM6A). We report on a male with developmental delays, cleft palate, craniofacial dysmorphism, hypotonia, and central nervous system anomalies including diminished white matter with thinning of the corpus callosum. Exome sequencing revealed a de novo mutation in ANKRD11, c.2606_2608delAGA, predicting p.Lys869del and an additional, de novo mutation, c.2353T>C, predicting p.Tyr785His in KDM1A, a gene not previously associated with a human phenotype. We describe this child as the first report of a deleterious sequence variant in KDM1A and hypothesize that his phenotype resulted from the combined effect of both mutations.
Department of Pediatrics and Institute for Human Genetics, University of California, San Francisco, San Francisco, California.
Sanjin
S
Tunovic
James
J
Barkovich
Elliott H
EH
Sherr
Anne M
AM
Slavotinek
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000175:diagnosis* / Q000235:genetics*; D001921:Brain / Q000473:pathology; D005145:Face / Q000002:abnormalities*; D019066:Facies; D006402:Hematologic Diseases / Q000175:diagnosis* / Q000235:genetics*; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D014071:Tooth Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D015837:Vestibular Diseases / Q000175:diagnosis* / Q000235:genetics*
C492515:ANKRD11 protein, human; D012097:Repressor Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human
ANKRD11; KBG syndrome; KDM1A; KDM6A; Kabuki syndrome