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De novo ANKRD11 and KDM1A gene mutations in a male with features of KBG syndrome and Kabuki syndrome
Author(s) -
Tunovic Sanjin,
Barkovich James,
Sherr Elliott H.,
Slavotinek Anne M.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36450
Subject(s) - kabuki syndrome , haploinsufficiency , genetics , biology , exome sequencing , phenotype , missense mutation , hypotonia , gene
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. © 2014 Wiley Periodicals, Inc.