Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous...

Area of Science:

• Genetics
• Dermatology
• Oncology

Background:

• Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare genetic disorders with overlapping clinical features.
• Previously, these conditions were suspected to be mosaic disorders, but definitive genetic evidence was limited.

Observation:

• This study investigated the molecular genetic basis of OES and ECCL in four patients (three with OES, one with ECCL).
• DNA analysis of lesional tissue was performed using Sanger sequencing of the KRAS gene.

Findings:

• Somatic mutations in KRAS codon 146 (p.Ala146Val, p.Ala146Thr) were identified in all four patients at varying levels of mosaicism.
• These findings confirm OES as a mosaic RASopathy and establish a common genetic etiology for OES and ECCL.
• The identified KRAS mutations are known oncogenic variants with distinct functional impacts.

Implications:

• The study supports a shared genetic origin for OES and ECCL, linked to mosaic KRAS mutations.
• Phenotypic variability in mosaic RASopathies may be influenced by both the specific genotype and the distribution of mutated cells.
• This research advances the understanding of RASopathies and their complex genotype-phenotype correlations.