Noonan syndrome-like phenotype associated with an ERF frameshift variant

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Noonan syndrome is a RASopathy with known genetic causes in 80-90% of cases.
• ETS2 repressor factor (ERF) variants are linked to syndromic craniosynostosis.
• The molecular mechanisms underlying Noonan syndrome remain incompletely understood.

Observation:

• A family presented with a Noonan syndrome-like phenotype, including short stature, distinctive facial features, and developmental delay.
• Exome sequencing revealed a heterozygous ERF frameshift variant (c.185del) in the proband and affected family members.
• The identified ERF variant cosegregated with the Noonan syndrome-like phenotype within the family.

Findings:

• This study reports a novel heterozygous ERF frameshift variant associated with a Noonan syndrome-like phenotype.
• The ERF variant identified in the family was previously linked to syndromic craniosynostosis.
• Clinical features observed in the affected family members overlap significantly with those of Noonan syndrome.

Implications:

• This finding expands the known genetic spectrum of Noonan syndrome.
• Heterozygous ERF variants are implicated as a potential cause of Noonan syndrome-like phenotypes.
• Further research into ERF's role in the RAS/MAPK pathway may elucidate Noonan syndrome pathogenesis.