Novel Variants in KMT2C Further Support a Neurodevelopmental Disorder Distinct From Kleefstra and Kabuki Syndromes

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Molecular Biology

Background:

• KMT2C gene variants are a recently identified cause of neurodevelopmental disorder.
• KMT2C-related disorder presents with developmental delay, intellectual disability, and behavioral issues.
• This condition is distinct from Kleefstra and Kabuki 1 syndromes.

Purpose of the Study:

• To describe the detailed phenotypes of three patients with novel KMT2C gene variants.
• To expand the known spectrum of KMT2C causal variants.
• To further characterize KMT2C-related neurodevelopmental disorder.

Main Methods:

• Exome sequencing was used to identify variants in the KMT2C gene.
• Phenotype analysis was conducted on three patients.
• Comparison with previously reported cases was performed.

Main Results:

• Two heterozygous variants (c.3212G>A, p.(Trp1071*) and c.13204_13205delinsA, p.(Cys4402Ilefs*11)) and one missense variant (c.6517C>T, p.(Pro2173Ser)) in KMT2C were identified.
• Patients exhibited developmental delay, speech delay, autism spectrum disorder, cognitive impairment, seizures, and craniofacial dysmorphism.
• The identified variants lead to premature stop codons or altered protein sequences.

Conclusions:

• The phenotypes of the studied patients align with previously described KMT2C-related neurodevelopmental disorder.
• These findings further extend the list of KMT2C causal variants.
• The patients' phenotypes are consistent with KMT2C-related Kleefstra syndrome 2.