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Somatic KRAS mutation affecting codon 146 in linear sebaceous nevus syndrome
Saloni Kapoor1, Hannah L Scanga1, Miguel Reyes-Múgica1
1UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
American Journal of Medical Genetics. Part A
|July 13, 2021
Summary
Linear Sebaceous Nevus Syndrome, a rare mosaic RASopathy, is linked to KRAS mutations. These findings suggest LSNS, OES, and ECL are part of a disease spectrum.
Area of Science:
- Genetics
- Developmental Biology
- Dermatology
Background:
- Linear Sebaceous Nevus Syndrome (LSNS) is a rare congenital disorder.
- LSNS is characterized by nevus sebaceus and associated ectodermal and central nervous system abnormalities.
- It is hypothesized to be a mosaic RASopathy, resulting from postzygotic mutations in the RAS/MAPK signaling pathway.
Observation:
- Two patients with LSNS were identified.
- Both patients exhibited mutations in codon 146 of the KRAS gene.
- Mosaicism was confirmed in the affected individuals.
Findings:
- The identified KRAS mutations in LSNS patients are identical to those previously reported in Oculoectodermal Syndrome (OES) and Encephalocraniocutaneous Lipomatosis (ECL).
- OES and ECL are also classified as mosaic RASopathies with significant cerebrooculocutaneous features.
- This genetic overlap indicates a shared etiology between LSNS, OES, and ECL.
Implications:
- The findings suggest that LSNS, OES, and ECL may represent a spectrum of related disorders rather than distinct entities.
- This reclassification has significant implications for diagnosis, genetic counseling, and patient management.
- A unified approach to evaluating and managing these conditions as a spectrum is recommended.
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