The First Missense Pathogenic Variant in the KAT6A Gene

A KAT6A Variant in a Family with Autosomal Dominantly Inherited Microcephaly and Developmental Delay

CENTOGENE published results of another successful collaborative study in the highly ranked Journal of Human Genetics titled: “A KAT6A variant in a family with autosomal dominantly inherited microcephaly and developmental delay.”

This study reports the first missense pathogenic variant in the KAT6A gene causing severe developmental delay, intellectual disability and microcephaly. Using exome sequencing we identified a novel, dominantly inherited KAT6A pathogenic missense variant in an affected child and her mildly affected father. This report thus expands the spectrum of disease-causing variants in the KAT6A gene to also include missense variants in this gene.

J Hum Genet. 2018 Jun 13. doi: 10.1038/s10038-018-0469-0. [Epub ahead of print]


Approximately 1-3% of children have intellectual disability or global developmental delay. Heterozygous mutations have emerged as a major cause of different intellectual disability syndromes. In severely affected patients, reproductive fitness is impaired and mutations have usually arisen de novo. Massive parallel sequencing has been an effective means of diagnosing patients, especially those who carry a de novo mutation. The molecular diagnosis can be a way to shift from a more phenotype-driven management of the clinical signs to a more refined treatment based on genotype. Here, we report a novel dominantly inherited KAT6A missense variant in the C-terminal transactivation domain identified by exome sequencing in a girl and her father. Both had intellectual disability/developmental delay, short stature, microcephaly, and strabismus with the father being mildly affected. We here report the first inherited variant in KAT6A and suggest missense variants in KAT6A to be associated with an inheritable, milder clinical presentation compared to previously reported de novo, truncating mutations in this gene.


  • Joanne Trinh , Phd
  • Irina Hüning , MD
  • Zafer Yüksel , MD
  • N Baalmann
  • S Imhoff
  • Prof. Christine Klein , MD
  • Prof. Arndt Rolfs , MD
  • Prof. Gabriele Gillessen-Kaesbach , MD
  • Katja Lohmann , PhD

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