16q24.3 Microdeletions Disrupting Upstream Non-Coding Region of ANKRD11 Cause KBG Syndrome

Area of Science:

• Genetics
• Developmental Biology
• Molecular Biology

Background:

• KBG syndrome is a multisystem developmental disorder.
• It is characterized by specific physical and developmental features.
• Haploinsufficiency of the ANKRD11 gene causes KBG syndrome.

Purpose of the Study:

• To investigate the role of microdeletions in the non-coding exon 1 of ANKRD11.
• To analyze the impact of these deletions on ANKRD11 transcript levels and global transcriptome.
• To establish a link between these microdeletions and KBG syndrome.

Main Methods:

• Clinical case reporting of three individuals with KBG syndrome features.
• Molecular analysis of microdeletions encompassing ANKRD11 non-coding exon 1.
• Transcriptome analysis to assess gene expression alterations.

Main Results:

• Identified microdeletions in non-coding exon 1 of ANKRD11 in affected individuals.
• Observed reduced ANKRD11 transcript levels.
• Detected global transcriptome alterations consistent with KBG syndrome.

Conclusions:

• Microdeletions involving non-coding exon 1 of ANKRD11 are causative of KBG syndrome.
• Transcriptome analysis is a valuable tool for interpreting novel copy number variants in non-coding regions.
• This study highlights the importance of ANKRD11 non-coding regions in development.