An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and additional features expands the phenotype associated with mutations in KAT6B.
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant disorder caused by mutations in FOXL2. We identified an individual with BPES and additional phenotypic features who did not have a FOXL2 mutation. We used whole exome sequencing to identify a de novo mutation in KAT6B (lysine acetyltransferase 6B) in this individual. The mutation was a 2-bp insertion leading to a frameshift which resulted in a premature stop codon. The resulting truncated protein does not have the C-terminal serine/methionine transcription activation domain necessary for interaction with other transcriptional and epigenetic regulators. This mutation likely has a dominant-negative or gain-of-function effect, similar to those observed in other genetic disorders resulting from KAT6B mutations, including Say-Barber-Biesecker-Young-Simpson (SBBYSS) and genitopatellar syndrome (GTPTS). Thus, our subject's phenotype broadens the spectrum of clinical findings associated with mutations in KAT6B. Furthermore, our results suggest that individuals with BPES without a FOXL2 mutation should be tested for KAT6B mutations. The transcriptional and epigenetic regulation mediated by KAT6B appears crucial to early developmental processes, which when perturbed can lead to a wide spectrum of phenotypic outcomes.
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
Hung-Chun
HC
Yu
Elizabeth A
EA
Geiger
Livija
L
Medne
Elaine H
EH
Zackai
Tamim H
TH
Shaikh
D016569:Blepharophimosis / Q000235:genetics*; D018389:Codon, Nonsense; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics; D016368:Frameshift Mutation; D051548:Histone Acetyltransferases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012868:Skin Abnormalities / Q000235:genetics*; D014564:Urogenital Abnormalities
D018389:Codon, Nonsense; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D051548:Histone Acetyltransferases; C487137:KAT6B protein, human
BPES; KAT6B; blepharophimosis; epicanthus inversus; ptosis; whole exome sequencing