Splicing and frameshift variants in QSER1 may be involved in developmental phenotypes.

Area of Science:

• Genetics
• Developmental Biology
• Human Disease

Background:

• Human development relies on precise gene regulation by proteins.
• Heterozygous variants in PRR12 cause a spectrum of developmental disorders.
• QSER1 is a paralog of PRR12, sharing conserved regions and implicated in gene regulation.

Purpose of the Study:

• To investigate the role of QSER1 in human neurodevelopmental phenotypes.
• To identify and characterize variants in QSER1 associated with developmental anomalies.

Main Methods:

• Genetic analysis of three unrelated individuals with neurodevelopmental phenotypes.
• Identification and characterization of QSER1 variants (frameshift, splice site).
• In silico predictions and minigene assays to assess variant effects.
• In situ hybridization in zebrafish to study qser1 expression patterns.

Main Results:

• Three individuals presented with neurodevelopmental phenotypes and heterozygous QSER1 variants.
• Identified two novel de novo frameshift alleles and one splice site variant.
• Splice site variant led to abnormal transcripts, including frameshift and in-frame deletion.
• Zebrafish studies showed broad qser1 expression, particularly in the developing brain.

Conclusions:

• Heterozygous QSER1 variants are associated with human neurodevelopmental disorders and multisystem anomalies.
• QSER1 plays a role in vertebrate development, potentially through regulation of gene expression.
• Further research into QSER1 function is warranted to understand its contribution to human disease.