Case report: A novel FBXW7 gene variant causes global developmental delay.

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• The FBXW7 gene plays a crucial role in cell cycle regulation and tumor suppression.
• Mutations in FBXW7 have been associated with various cancers and developmental disorders.
• Understanding FBXW7 mutations is vital for diagnosing and managing genetic conditions.

Observation:

• A 2-year-old male presented with global developmental delay, language impairment, and distinct facial dysmorphism.
• Clinical features included hypertonia, labial hemangioma, hydrocele, and overgrowth.
• Whole-exome sequencing identified a novel de novo pathogenic variant in the FBXW7 gene (c.1612C>T).

Findings:

• The identified FBXW7 variant, c.1612C>T (p.Gln538*), represents a previously unreported locus.
• This pathogenic variant is linked to a rare genetic disorder characterized by developmental delay, hypotonia, and impaired language (OMIM: #620012).
• The case expands the known spectrum of FBXW7-related pathogenic variants.

Implications:

• This case underscores the phenotypic heterogeneity of FBXW7-related disorders.
• The presence of hypertonia, labial hemangioma, and hydrocele suggests a broader clinical presentation than previously recognized.
• Identifying novel mutations enriches our understanding of FBXW7's role in neurodevelopment and disease.