16p11.2 de novo microdeletion encompassing SRCAP gene in a patient with speech impairment, global developmental...

Area of Science:

• Genetics
• Neurodevelopmental Disorders
• Human Genetics

Background:

• 16p11.2 microdeletions are associated with various neurodevelopmental and behavioral phenotypes.
• Floating-Harbor syndrome (FHS) is a rare genetic disorder caused by mutations in the SRCAP gene.
• The SRCAP gene (OMIM*611421) plays a role in transcriptional regulation and chromatin remodeling.

Observation:

• A patient presented with speech impairment, global developmental delay, and behavioral issues due to a de novo 186 kb microdeletion on 16p11.2.
• This deletion encompasses nine RefSeq genes, including SRCAP, and is the first reported instance of a 16p11.2 deletion fully removing one copy of SRCAP.
• The patient exhibited subtle features reminiscent of FHS, though not meeting the diagnostic criteria.

Findings:

• Haploinsufficiency of the SRCAP gene, due to the deletion of one copy, is suggested as a potential cause for the observed phenotype.
• The patient's symptoms of speech impairment, global developmental delay, and behavioral problems align with potential SRCAP haploinsufficiency.
• Subtle phenotypic features resembling FHS were noted, but a definitive clinical diagnosis was not possible based on facial characteristics.

Implications:

• This case suggests that isolated SRCAP deletion via 16p11.2 microdeletion may contribute to a spectrum of neurodevelopmental and behavioral issues.
• Further research is needed to confirm the causative role of SRCAP isolated deletion in these phenotypes.
• Understanding the role of SRCAP haploinsufficiency expands knowledge of 16p11.2 deletion syndrome and its genetic underpinnings.